Distally Predominant, Symmetrical, Axonal

Polyneuropathies an overview

Introduction
The words Neuropathy, Polyneuropathy and Peripheral Neuropathy actually
encompass many different disorders. They may include systemic, infectious or
inflammatory causes. These several categories could include hereditary motor and
sensory neuropathies or acquired neuropathies secondary to toxic exposure or even as a
side effect of some drugs.

This paper focuses on the distally predominant, symmetrical and primarily axonal
neuropathies (DSPN) that are common in the NCS/EMG laboratory and are associated
with systemic or metabolic diseases such as diabetes. This is not to discount all the other
findings and symptoms of polyneuropathies. Other causes of neuropathy as well as
hereditary causes will be addressed in subsequent papers.

Diabetic polyneuropathy is the most common polyneuropathy in the United States. Other
causes of systemic and metabolic causes of polyneuropathy might include renal failure,
uremia, hepatic disorders and critical care illnesses.

This paper will look at the clinical presentation, differential diagnosis, specifics of
NCS/EMG testing and case studies.

Clinical Presentation
Diabetes is not a new condition and the relative association to nervous system changes
has been evident for more than a century and a half. Loss of deep tendon reflexes and
impaired vibration in the lower extremities in patients with a long history of diabetes is
well documented. Studies show that half to two-thirds of all diabetic patients will suffer
from neuropathy. Varying degrees of both small and large fiber involvement is seen.

Occasionally a very mild or asymptomatic polyneuropathy is discovered in the EMG lab

when investigating another group of symptoms, such as carpal tunnel syndrome. More
often, however, patients present with a variety of symptoms that suggest peripheral nerve
disease, such as distal paresthesias.

The symptoms may take years to develop. Distal paresthesias and distal weakness are the
most common complaints. Loss of vibratory and position sense can be present, but is less
common. It is believed that the distal predominance is related to the axon length; the
longer the axon the greater it is affected. It is generally accepted when the paresthesias
reach approximately mid-calf, sensory symptoms become evident in the hands. This is
referred to as the stocking-glove distribution. Motor involvement with frank weakness
can occur in the same pattern, but only later and in more severe cases.
On examination, distal loss of sensation to pin prick, light touch, vibration, cold and
proprioception occur in the stocking-glove distribution and tends to be similar to the
subjective complaints. Decreased or absent ankle reflexes occur early in the disease,
while more widespread loss of reflexes and motor weakness are late findings. Motor
examination may disclose wasting of the intrinsic muscles of the feet or lower leg; similar
findings are evident in the hands in more severe cases.

Differential Diagnosis
The key in separating distally predominant, symmetrical axonal neuropathies from other
conditions are time course, the sensory more than motor symptoms and the symmetry of
the symptoms.

Guillain-Barr has an acute and rapid onset, while CIDP has a gradual onset. The
inclusion of motor symptoms helps it stand out versus DSPNs. Mononeuropathy
multiplex can closely resemble DSPN but is not symmetrical. Mononeuropathy multiplex
presents with multiple mononeuropathies with involvement of entirely unrelated nerves,
such as the median nerve in the arm and the tibial nerve in the leg. If more proximal signs
are present alarm bells should ring for an alternate or secondary cause.

Specific Nerve Conduction Studies

The most common way to sort out these different types of polyneuropathies is the
NCS/EMG. There are specific and fairly standard test protocols for DSPN.

It is generally accepted that NCS examination of 3 extremities is required to prove distal

predominance and symmetry. Unless there is a compelling reason to choose otherwise
(i.e. leg amputation) these limbs would include both legs and one arm. If an asymmetry
exists, additional or alternate explanations could necessitate additional testing.

In the legs:
The sural sensory nerve is important as it is a long and a purely sensory nerve. In a
patient with a DSPN one would expect reduced amplitude with a normal or very near
normal latency and/or conduction velocity. As the disease progresses the sural sensory
nerve may be non-recordable. In general, these findings hold true for additional sensory
nerves you may examine. The superficial peroneal and medial plantar nerves may be
useful especially when looking for mild DSPN. Averaging of the lower extremity sensory
responses is often necessary and many labs average routinely.

The peroneal motor nerve (sometimes called fibular nerve) should be recorded over the
extensor digitorum brevis (EDB). The three standard stimulation sites, ankle, fibular head
and above knee sites should be recorded. The findings may stay in the normal range in
the earliest stages of DSPN. Reduced amplitude with normal or near normal latencies and
conduction velocities are the usual findings in modest DSPN, while additional amplitude
reduction and CV slowing in all segments is seen as the disease progresses. If the
response to the EDB is absent or very low amplitude the peroneal nerve recording from
the tibialis anterior (TA) is useful as it is more proximal. It is logical that the CMAP
amplitude would be greater when recording over the TA. If, on this examination, focal
conduction velocity slowing or a focal conduction block is seen, consider an alternative
or an additional problem (i.e. peroneal neuropathy at the fibular head).

Peroneal F-wave is considered helpful in separating proximal from distal conditions and
is usually mildly prolonged is DSPNs. The peroneal F-wave, however, can be fickle and
is not always recordable, especially if there is reduced distal amplitude.

The tibial motor nerve is recorded over the abductor hallucis (AH) and stimulated at the
ankle, behind the medial malleolus, and in the popliteal fossa. The findings may stay in
the normal range in the earliest stages of DSPN. Reduced amplitude with normal or near
normal latencies and conduction velocities are common as the disease progresses. The
tibial CMAP seems to remain normal or near normal well into the disease process.

Tibial F-wave is considered helpful in separating proximal from distal conditions and is
usually mildly prolonged is DSPNs.

To evaluate and prove symmetry at least one sensory and one motor nerve should be
done on the opposite leg. If asymmetries (i.e. amplitude differences of more than 50%)
are observed, additional testing would be indicated.

In the arms:
The median sensory nerve should be studied in your usual fashion, either antidromically
or orthodromically. The longer segment from the wrist to digit II or III (12-14 cm) is
preferable to the palmar studies. In a patient with a DSPN one would expect reduced
amplitude with a normal or very near normal latency and/or conduction velocity. It is
expected this reduced amplitude, however, would be less dramatic than the amplitude
reduction of the sural or superficial peroneal nerves in the legs.

The ulnar sensory nerve should be studied in your usual fashion, either antidromically or
orthodromically. The longer segment from the wrist to digit V (11-13 cm) is preferable to
the palmar studies. In a patient with a DSPN one would expect reduced amplitude with a
normal or very near normal latency and/or conduction velocity. It is expected this
reduced amplitude, however, would be less dramatic than the amplitude reduction of the
sural or superficial peroneal nerves in the legs.

The radial sensory nerve should be studied in your usual fashion and is useful because
both the median and ulnar nerves are prone to entrapment neuropathies and the radial less
so. In a patient with DSPN, reduced amplitude may be present and this reduction
becomes more obvious as the disease progresses. Latency and/or conduction velocity is
generally preserved.

There is a well documented increased incidence of carpal tunnel syndrome in patients

with distally predominant, symmetrical axonal neuropathies. Thus if there is a prolonged
 distal latency of the median nerve a further examination such as the transcarpal, median
to ulnar comparison may be indicated.

The median motor nerve should be studied recording over the abductor pollicis brevis
(APB). Stimulation at the wrist and elbow should be recorded. The findings remain
normal in early DSPN and usually only show amplitude reduction in the most advanced
cases. If a prolonged latency is present consider the possibility of an underlying
condition, such as carpal tunnel syndrome.

Median F-wave is considered helpful in separating proximal from distal conditions and is
usually mildly prolonged is DSPNs. Care should be taken when a CTS is present as the
prolonged F-wave may simply indicate the slowing in the distal segment.

The ulnar motor nerve should be studied recording over the abductor digiti minimi
(ADM). Stimulation at the wrist, below and above the elbow should be recorded. The
findings remain normal in early DSPN and usually only show amplitude reduction in the
most advanced cases. If slowed conduction velocity or focal amplitude reduction is
present consider the possibility of an underlying conduction, such as ulnar neuropathy at
the elbow.

Ulnar F-wave is considered helpful in separating proximal from distal conditions and is
usually mildly prolonged is DSPNs. Care should be taken when an ulnar neuropathy is
present as the prolonged F-wave may simply indicate the slowing in the across elbow
segment.

Case Studies

Case 1

Mild distally predominant, symmetrical and primarily axonal neuropathy

Temperatures:
Date of Birth: 8/6/1948 Left wrist: 32C
Age: 60 Right leg: 32.5C
Gender: Male Left leg: 33.5C

REASON FOR STUDY: History of right hand weakness and fasciculations in the proximal arms for many years.
Patient was recently diagnosed with Parkinsonism and responded somewhat to Sinemet. Reflexes are reduced in the
left arm and can be elicited at both ankles. There is no pathological spread. The current study is requested to evaluate
for underlying neuropathic changes.

CLINICAL CORRELATION:

There is electrical evidence to suggest the presence of a mild, generalized, length-dependent, relatively symmetric,
predominately sensory axonal polyneuropathy. The differential diagnosis of this pattern is extensive and includes
nutritional deficiencies, alcoholism, connective tissue disorders, toxic, metabolic and drug induced neuropathies,
HIV, lymphomatous and carcinomatous neuropathies, and selected other rare conditions.
 Abnormal values are in Bold
Motor Nerve Conduction:
Nerve and Site Segment Distance Latency Amplitude Conduction
Velocity
Right Peroneal
Ankle Extensor digitorum brevis-Ankle 90 mm 5.4 ms 2.02 mV
Fibula (head) Ankle-Fibula (head) 320 mm 12.5 ms 1.96 mV 45.0 m/s
Popliteal fossa Fibula (head)-Popliteal fossa 100 mm 14.5 ms 1.93 mV 50.0 m/s
Right Tibial
Ankle Abductor hallucis-Ankle 100 mm 5.0 ms 7.97 mV
Popliteal fossa Ankle-Popliteal fossa 445 mm 14.7 ms 4.96 mV 45.8 m/s
Left Peroneal
Ankle Extensor digitorum brevis-Ankle 90 mm 4.3 ms 4.91 mV
Fibula (head) Ankle-Fibula (head) 330 mm 11.9 ms 4.18 mV 43.4 m/s
Popliteal fossa Fibula (head)-Popliteal fossa 100 mm 13.9 ms 3.96 mV 50.0 m/s
Left Tibial
Ankle Abductor hallucis-Ankle 100 mm 4.4 ms 6.85 mV
Popliteal fossa Ankle-Popliteal fossa 430 mm 14.3 ms 4.13 mV 43.4 m/s
Left Median
Wrist Abductor pollicis brevis-Wrist 60 mm 3.4 ms 13.32 mV
Elbow Wrist-Elbow 265 mm 8.6 ms 13.18 mV 50.9 m/s
Axilla Elbow-Axilla 170 mm 11.6 ms 12.71 mV 56.6 m/s
Left Ulnar
Wrist ADM-Wrist 60 mm 2.7 ms 11.65 mV
Below elbow Wrist-Below elbow 265 mm 7.8 ms 10.61 mV 51.5 m/s
Above elbow Below elbow-Above elbow 100 mm 9.7 ms 9.86 mV 53.7 m/s
Axilla Above elbow-Axilla 135 mm 11.9 ms 9.58 mV 61.3 m/s

F-Wave Studies
Nerve M-Latency F-Latency
Right Peroneal 5.4 ms 57.3 ms
Right Tibial 5.0 ms 53.0 ms
Left Peroneal 4.3 ms 52.3 ms
Left Tibial 4.4 ms 55.1 ms
Left Median 3.4 ms 30.5 ms
Left Ulnar 11.9 ms 30.6 ms

Sensory Nerve Conduction:

Nerve and Site Segment Distance Amplitude Peak
Latency
Left Radial
Forearm Anatomical snuff box-Forearm 100 mm 19.8 V 2.4 ms
Left Sural
Lower leg Lateral malleolus-Lower leg 140 mm 3.0 V 3.6 ms
Right Sural
Lower leg Lateral malleolus-Lower leg 140 mm 2.6 V 3.8 ms
Left Superficial Peroneal
Lower leg Ankle-Lower leg 140 mm 4.1 V 3.6 ms
Right Superficial Peroneal
Lower leg Ankle-Lower leg 140 mm 4.1 V 3.6 ms
Left Median
Digit II (index finger) Wrist-Digit II (index finger) 130 mm 11.2 V 2.9 ms
Left Ulnar
Digit V (little finger) Wrist-Digit V (little finger) 110 mm 4.2 V 3.1 ms
 1 ms 1 ms 5 ms

Right Peroneal
A1 100mA

A1 A1 Left Superficial 1 mV

1 2 Left Sural 10 uV 1 2
Peroneal 10 uV
3 4 N: 4 3 4 N: 4

A2 34.5mA
1 mV

Right Superficial
B3 B3
1 2 Right Sural 10 uV 1 2 Peroneal 10 uV
3 4 N: 4 3 4 N: 4

A3 71.3mA
1 mV

o o o
Amp 1: 20-3kHz Temp: 21.2 C Amp 1: 20-3kHz Temp: 21.2 C Amp 1: 2-10kHz Temp: 21.2 C

1 mV F-SNS: 50 uV 10 ms 5 ms 5 mV F-SNS: 500 uV 10 ms

71.3mA Right Tibial 100mA

71.3mA 100mA

71.3mA 100mA
A1 51.7mA
71.3mA 5 mV 100mA

71.3mA 100mA

71.3mA 100mA

71.3mA 100mA

71.3mA 100mA

71.3mA 100mA

71.3mA 100mA

71.3mA

A2 100mA
5 mV

Right Tibial
Right Peroneal
F-wave
F-wave

Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C

2 ms 2 mV F-SNS: 200 uV 10 ms 2 ms

Left Peroneal 100mA

Left Tibial
100mA
A1 100mA
2 mV 100mA
A1 100mA
100mA 2 mV

100mA

100mA

100mA

100mA
A2 100mA
2 mV 100mA

A2 100mA
Left Peroneal 2 mV

F-wave
A3 100mA
2 mV

Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C
 5 mV F-SNS: 500 uV 10 ms 2 ms 5 mV F-SNS: 500 uV 5 ms

100mA
Left Median 100mA

100mA 100mA
A1 82.3mA
100mA 5 mV 100mA

100mA 100mA

100mA 100mA

100mA 100mA

100mA 100mA

100mA 100mA
A2 74.5mA
100mA 5 mV 100mA

100mA 100mA

Left Tibial
F-wave A3 100mA
Left Median
5 mV
F-wave
Amp 1: 2-10kHz Temp: 21.4 o C Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C

1 ms 2 ms 5 mV F-SNS: 500 uV 5 ms
Left Ulnar
100mA
Left Median
100mA
Orthodromic A1 100mA
5 mV 100mA
A1
1 2 10 uV 100mA
3 4 N: 4
100mA

100mA
A2 100mA
5 mV 100mA

100mA

100mA

100mA
A3 55.6mA
Right Median 5 mV

Orthodromic
B3
1 2 10 uV
Left Ulnar
3 4 N: 4

A4 100mA
F-wave
5 mV

o
Amp 1: 20-3kHz Temp: 21.4 C Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C

Case 2

Moderate to severe distally predominant, symmetrical and primarily axonal neuropathy

Temperatures:
Date of Birth: 5/24/1940 Right wrist: 31.5C
Age: 69 Right leg: 31C
Gender: Male Left leg: 31.5C

REASON FOR STUDY: History of long-standing leg cramps and 5 year history of leg weakness. Evaluate
for underlying neuropathic or myopathic process.
CLINICAL CORRELATION:

This is an abnormal study. There is electrical evidence to suggest the presence of the presence of a
generalized, chronic, length-dependent, relatively symmetric, mixed sensory and motor axonal
polyneuropathy. The differential diagnosis of this pattern is extensive and includes nutritional deficiencies,
alcoholism, connective tissue disorders, toxic, metabolic and drug induced neuropathies, HIV,
lymphomatous and carcinomatous neuropathies, and selected other rare conditions.
Abnormal values are in Bold
Motor Nerve Conduction:
Nerve and Site Segment Distance Latency Amplitude Conduction
Velocity
Right Peroneal
Ankle Extensor digitorum brevis-Ankle 90 mm 7.4 ms 0.07 mV
Right Peroneal
Fibula (head) Tibialis anterior-Popliteal fossa 3.6 ms 1.37 mV
Popliteal fossa Fibula (head)-Popliteal fossa 100 mm 5.5 ms 1.35 mV 52.6 m/s
Right Tibial
Ankle Abductor hallucis-Ankle 100 mm 5.6 ms 0.41 mV
Popliteal fossa Ankle-Popliteal fossa 420 mm 14.2 ms 0.28 mV 48.8 m/s
Right Median
Wrist Abductor pollicis brevis-Wrist 60 mm 4.2 ms 6.08 mV
Elbow Wrist-Elbow 270 mm 9.7 ms 5.63 mV 49.0 m/s
Right Ulnar
Wrist ADM-Wrist 60 mm 3.2 ms 5.48 mV
Below elbow Wrist-Below elbow 240 mm 8.0 ms 5.50 mV 50.0 m/s
Above elbow Below elbow-Above elbow 100 mm 9.9 ms 5.39 mV 52.6 m/s
Left Peroneal
Ankle Extensor digitorum brevis-Ankle 90 mm 6.6 ms 0.09 mV
Left Peroneal
Fibula (head) Tibialis anterior-Popliteal fossa 3.8 ms 0.96 mV
Popliteal fossa Fibula (head)-Popliteal fossa 100 mm 5.6 ms 0.88 mV 55.5 m/s
Left Tibial
Ankle Abductor hallucis-Ankle 100 mm 5.6 ms 0.32 mV

Sensory Nerve Conduction:

Nerve and Site Segment Distance Amplitude Peak
Latency
Left Sural
Lower leg Lateral malleolus-Lower leg 140 mm NR NR
Right Sural
Lower leg Lateral malleolus-Lower leg 140 mm NR NR
Right Superficial Peroneal
Lower leg Ankle-Lower leg 140 mm NR NR
Right Median
Digit II (index fing Wrist-Digit II (index finger) 130 mm 5.5 V 3.7 ms
Right Ulnar
Digit V (little fing Wrist-Digit V (little finger) 110 mm 4.0 V 2.8 ms
Right Transcarpal, Med-Uln Comparison
Mid palm (Median) Wrist-Mid palm (Median) 80 mm 15.0 V 2.5 ms
Mid palm (Ulnar) Wrist-Mid palm (Ulnar) 80 mm 5.6 V 2.0 ms
Right Radial
Forearm Anatomical snuff box-Forearm 100 mm 12.1 V 2.7 ms
Stim: 1
1 ms 1 ms 2 ms

Right Peroneal - EDB

Left Sural A1 100mA

200 uV
A1 A1
1 2 10 uV 10 uV
3 4 N: 4

A2 Right Peroneal - TA
200 uV

A3
200 uV

B5 100mA
200 uV
B3 B3 Right Superficial
1 2
3 4 Right Sural 10 uV
N: 4
1 2
3 4
Peroneal
10 uV
N: 4

B6 63.5mA
200 uV

Amp 1: 20-3kHz Temp: 21.4 o C Amp 1: 20-3kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C
N N Oh Sid SNC MUNE
5 ms 1 ms 1 ms

Right Tibial
Right Median
A1 100mA A1 A1
100 uV 1 2 10 uV 10 uV
3 4 N: 4

Right Ulnar Right Radial

A2 100mA B3 B3
100 uV 1 2 10 uV 1 2 10 uV
3 4 N: 4 3 4 N: 4

Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 20-3kHz Temp: 21.3 o C Amp 1: 20-3kHz Temp: 21.3 o C
2 ms 2 ms 2 ms

Right Median Right Ulnar Left Peroneal - EDB

A1 100mA A1 100mA
2 mV 200 uV
A1 100mA
5 mV

A2
500 uV

Left Peroneal - TA
A2 40.7mA A3
2 mV 500 uV

B5 100mA
500 uV
A2 100mA
5 mV

A3 43.1mA B6 100mA
2 mV 500 uV

o
Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.3 o C Amp 1: 2-10kHz Temp: 21.4 C
2 ms

Left Tibial

A1 100mA
200 uV
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