This document provides an overview of peripheral neuropathy, including:
- Types of peripheral neuropathy are classified based on whether they primarily affect motor nerves, sensory nerves, or both.
- The main symptoms of motor, sensory, and autonomic neuropathies are described.
- The most common causes of peripheral neuropathy include systemic disorders like diabetes, connective tissue diseases, nutritional deficiencies, infections, malignancies and toxic neuropathies.
- The approach to evaluating a patient with peripheral neuropathy involves obtaining a history, neurological exam, electrodiagnostic studies and sometimes nerve biopsy to identify the location and cause of the neuropathy.
2. Introduction
⢠Generalized term including disorders of any cause affecting PNS
⢠May involve sensory nerves, motor nerves, or both
⢠May affect one nerve (mononeuropathy), several nerves together (polyneuropathy)
or several nerves not contiguous (Mononeuropathy multiplex)
⢠Further classified into those that primarily affect the cell body (e.g., neuronopathy
or ganglionopathy), myelin (myelinopathy), and the axon (axonopathy)
4. Motor Symptoms
Loss of Functions â-
Symptomsâ
Disturbed Function â+
Symptomsâ
Motor Nerves: Large Fibre Wasting
Hypotonia
Weakness
Hyporeflexia
Fasciculation
Cramps
5. Sensory Symptoms
Loss of Functions â-
Symptomsâ
Disturbed Function â+
Symptomsâ
Sensory: Large Fibre Decreased Vibration
Decreased Proprioception
Hyporeflexia
Sensory Ataxia
Paresthesias
Sensory: Small Fibre Decreased Pain
Decreased Temperature
Dysesthesias
Allodynia
6. Autonomic Symptoms
Loss of Functions â-
Symptomsâ
Disturbed Function â+
Symptomsâ
Autonomic Nerves Decreased Sweating
Hypotension
Urinary retention
Impotence
Vascular color change
GI Complaints
Increased Sweating
Hypertension
11. Mononeuropathy
⢠Focal involvement of a single nerve and implies a local process:
⢠Direct trauma
⢠Compression or entrapment
⢠Vascular lesions
⢠Neoplastic compression or infiltration
12. Mononeuropathy Multiplex
⢠Simultaneous /sequential damage to multiple noncontiguous nerves.
⢠Ischemia caused by vasculitis
⢠Microangiopathy in diabetes mellitus
⢠Less common causes : Granulomatous, leukemic, or neoplastic infiltration,
Hansen's disease (leprosy) and sarcoidosis.
13. Polyneuropathy
⢠Characterized by symmetrical, distal motor and sensory deficits that have a graded
increase in severity distally and by distal attenuation of reflexes,
⢠Rarely predominantly proximal:(E.g: acute intermittent porphyria).
⢠The sensory deficits generally follow a length-dependent stocking-glove pattern
14.
15. Axonopathies
⢠By far the majority of the toxic, metabolic and endocrine causes
⢠NCVs: CMAPs â 80% lower limit of normal w/o or min velocity or distal motor
latency change.
⢠Legs>> arms.
⢠EMG: Signs of denervation (acute, chronic) and reinnervation
16. Myelinopathies
⢠Unusual by comparison with axonopathies
⢠Clues
⢠hypertrophic nerves on exam, global areflexia, weakness without wasting, motor >> sensory
deficits
⢠NCS
⢠Distal motor latency prolonged (>125% ULN), Conduction velocities slowed (<80% LLN)
May have conduction block
⢠EMG
⢠Reduced recruitment w/o much denervation
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20. Approach
⢠In approaching a patient with a neuropathy, the clinician has three main goals:
⢠identify where the lesion is,
⢠identify the cause, and
⢠determine the proper treatment.
⢠The first goal is accomplished by obtaining a thorough history, neurologic
examination, and electrodiagnostic and other laboratory studies. While gathering
this information, seven key questions are asked, the answers to which can usually
identify the category of pathology that is present.
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25. Evaluation
⢠Mild symptoms with known underlying lesion like DM, chemotherapy, alcohol
abuse â No evaluation is required
⢠Feature warranting a full evaluation
⢠Assymetry
⢠Non length dependence
⢠Motor predominance
⢠Acute onset
⢠Predominant autonomic involvement
⢠Rapidly progressive symptoms
⢠Sensory ataxia
29. History
⢠The temporal course of a neuropathy varies, based on the etiology.
⢠With trauma or ischemic infarction, the onset will be acute, with the most severe symptoms at
onset.
⢠Inflammatory and some metabolic neuropathies have a subacute course extending over days to
weeks.
⢠A chronic course over weeks to months is the hallmark of most toxic and metabolic
neuropathies.
30. ContdâŚ
⢠A chronic, slowly progressive neuropathy over many years occurs with most
hereditary neuropathies or with chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP).
⢠Neuropathies with a relapsing and remitting course include CIDP, acute porphyria,
Refsum's disease, hereditary neuropathy with liability to pressure palsies (HNPP),
familial brachial plexus neuropathy, and repeated episodes of toxin exposure.
31. ContdâŚ
⢠Ischemic neuropathies often have pain as a prominent feature.
⢠Small-fiber neuropathies often present with burning pain, lightning-like or
lancinating pain, aching, or uncomfortable paresthesias (dysesthesias).
⢠Dying-back (distal symmetric axonal) neuropathies initially involve the tips of the
toes and progress proximally in a stocking-glove distribution.
⢠Peripheral neuropathy can present as restless leg syndrome.
⢠Proximal involvement may result in difficulty climbing stairs, getting out of a
chair, lifting and bulbar involvement can also be seen
40. Recommendations for Lab Testing
⢠Screening laboratory tests may be considered for all patients with DSP.
⢠Tests with the highest yield of abnormality:
⢠Blood glucose (fasting)
⢠Serum B12 with metabolites (methylmalonic acid, homocysteine)
⢠SPEP(serum protein electrophoresis).
41. Other Laboratory Studies
⢠ANA, RF, Anti-dsDNA, Anti-Ro, Anti-La, ANCA screen, cryoglobulins
⢠Urine for heavy metals, porphyrins
⢠IFE/urine IFE/ plasma light chain analysis
42. Neuropathies + Serum Autoantibodies
⢠Antibodies against Gangliosides
⢠GM1 : Multifocal motor neuropathy
⢠GM1, GD1a : Guillain-BarrÊ syndrome
⢠GQ1b : Miller Fisher variant
⢠Antibodies against Glycoproteins
⢠Myelin-associated glycoprotein : MGUS
⢠Antibodies against RNA-binding proteins
⢠Anti-Hu, antineuronal nuclear antibody 1: Malignant inflammatory polyganglionopathy
46. Laboratory Evaluation
⢠The limitations of EMG/NCS should be taken into account when interpreting the
findings.
⢠There is no reliable means of studying proximal sensory nerves.
⢠NCS results can be normal in patients with small-fiber neuropathies
⢠Lower extremity sensory responses can be absent in normal elderly patients.
⢠EMG/NCS are not substitutes for a good clinical examination.
47. Nerve Biopsy
⢠In vasculitis, amyloid neuropathy, leprosy, CIDP, Inherited disorders of myelin,
and rare axonopathies
⢠The Sural nerve is selected most commonly
⢠The superficial peroneal nerve â alternative; :advantage of allowing simultaneous
biopsy of the peroneus brevis muscle through the same incision.
⢠This combined nerve and muscle biopsy procedure increases the yield of
identifying suspected vasculitis.
48.
49. Skin Biopsy
⢠Small fibre neuropathy
⢠Very small piece of skin just proximal to ankle is removed.
⢠Special stains are applied: Qualitative assessment or by careful counting to
determine intraepidermal nerve fibre.
52. Clinical Details
A 46 year old male presented with progressive asymmetric painful weakness of both upper limbs, 6 months
before presentation. Illness started with low grade fever and dry cough. He was evaluated, diagnosed and treated
for dengue fever and enteric fever based on his serological investigations, but there was no improvement.
Subsequently, he noticed difficulty in buttoning his shirt, beginning with the right hand and later affecting the
left hand as well. He was not able to perceive objects fully in palmer aspects of both hands. He significantly lost
weight. There is no lower limb weakness, bowel and bladder symptoms, nor any cranial nerve involvement. He
did not remember being exposed to drugs and toxins. Family history was not contributory. Examination
confirmed wasting, asymmetric sensory motor weakness, neurogenic tremor and depressed reflexes in both
upper limbs.
53. Clinical Details
In view of asymmetrical painful neurogenic weakness, EDX study was performed. It showed evidence of
multifocal sensory motor axonal neuropathy. His investigations showed eosinophilia. His ANA, ANA profile,
APLA, rheumatoid factor, sputum and BAL for AFB, serology for HBsAg, HCV and HIV were negative. His
blood sugar, renal function tests, thyroid function test, ECG, CSF, USG abdomen and MRI of the brain and
spine were normal. His p-ANCA was positive and CT thorax showed bronchopneumonia.
54. Discussion
This patient had painful sensory motor multiple mononeuropathies. Differentials of multiple neuropathies
(mononeuritis multiplex) are listed in the table below:
Diseases Clinical Clues
Leprosy Usually painless (pain can occur in lepromatous leprosy), h/o painless wounds,
hypoasthetic and hypopigmented skin patches and thickened nerves.
Diabetes Mellitus Painful, predominant sensory neuropathy and mild motor manifestations can
occur.
HIV Painful, sensory >> motor neuropathy
Vasculitis Painful, sensory and motor affection, may be present with features of systematic
vasculitis, elevated ESR, autoimmune panel may show a specific marker.
MADSAM Sensory-motor, upper limb predominant, proximal + distal polyneuropathy.
Prominent sensory symptoms in extremities, more common in females fourth
decade.
MMN Painless, pure motor neuropathy affecting upper limb.
Multiple Compression
Neuropathies
Painless, sensory-motor, multiple mononeuropathies. Electrophysiology shows
conduction slowing across compression sites. It occur in diabetes, hypothyroidism
and HNPP
55. ContdâŚ
Clinical electrophysiological and biochemistry profile strongly suggest possibility of vasculitis. Nerve biopsy
helps to confirm neuritis and also rule out close differentials. He underwent right superficial radial nerve biopsy
which showed moderate chronic, non uniform axonal neuropathy with mild perivascular inflammation and
hemosiderin deposition suggestive of vasculitic neuropathy.
Rheumatological evaluation showed systemic vasculitis process (CT thorax and ENT examination and
eosinophilia).
Final Diagnosis: ANCA-Associated vasculitis
56. Reference List
⢠Bradley and Daroffâs Neurology in Clinical Practice: 8th Edition.
⢠Harrisonâs Principles of Internal Medicine: 20th Edition.
⢠Amato AA, Russell J: Neuromuscular Disorder 2nd Edition, New York, Mc Graw
Hill, 2016.
⢠Pattern Recognition Approach to Neuropathy and Neuronopathy. Neurol Clin
31:343, 2013.
⢠Evaluation of Distel Symmetric Polyneuropathy: The Role of Laboratory and
Genetic Testing. Muscle Nerve 48:604, 2013.
