Distal Sensorimotor Polyneuropathy in Mature Rottweiler Dogs
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Vet Pathol 31:316-326 (1994)
Distal Sensorimotor Polyneuropathy in
Mature Rottweiler Dogs
K. G. BRAUND,M. TOIVIO-KINNUCAN, J. M. VALLAT,
J. R. MEHTA,AND D. C. LEVESQUE
Neuromuscular Laboratory, Scott-Ritchey Research Center (KGB, JRM), and Department of Pathobiology (MTK),
Auburn University College of Veterinary Medicine, Auburn, AL;
Veterinary Neurological Center, Phoenix, AZ (DCL); and
Service dc Neurologic, H6pital Univcrsitaire Dupuytren, Limoges, France (JMV)
Abstract. A polyneuropathy recognized in mature Rottweiler dogs is characterized by paraparesis that
progresses to tetraparesis, spinal hyporeflexia and hypotonia, and appendicular muscle atrophy. Although signs
may appear acutely, the course tends to be gradually progressive (up to 12 months or longer in some dogs) and
may be relapsing. Nerve and muscle biopsies were examined from eight affected Rottweilers (six male and two
female) between ages 1.5 and 4 years. Pronounced neurogenic atrophy was present in skeletal muscle samples.
Changes in sensory and motor peripheral nerves included loss of myelinated nerve fibers, axonal necrosis, and
variable numbers of fibers with inappropriately thin myelin sheaths. Ultrastructural findings included myelinated
fibers showing myelinoaxonal necrosis, demyelinated fibers often associated with macrophage infiltration, many
axons with myelinlike membranous profiles. increased endoneurial collagen, occasional axonal atrophy, and
numerous Bungner bands. Lesions in unmyelinated fibers included increased numbers of Schwann cell profiles
and loss of axons in Schwann cell subunits. Morphologic and morphometric studies indicated preferential loss
of medium (5.5-8 pm) and large (8.5-12.5 pm) fibers. which was more severe in distal parts of nerves than in
more proximal regions and nerve roots. The cause was not determined; however, histopathologic studies suggest
this condition is a dying-back distal sensorimotor polyneuropathy that has morphologic and morphometric
similarities to hereditary motor and sensory neuropathy (HMSN) type I1 in humans.
Key words: Animal model; distal axonopathy; dogs; dying-back polyneuropathy; HMSN type 11; morphom-
etry; muscle; nerve; teased fibers; ultrastructure.
Several neurologic abnormalities have been reported detected in any dog. Although signs appeared acutely in two
in Rottweiler dogs, including leukoencephalopathy in dogs. the clinical course typically was slowly progressive (up
mature dogs,34.49.55
neuroaxonal dystrophy in immature to 12 months or longer in some dogs). In three dogs, the
and mature dogs,20.21.32an isolated case of polyneuritis clinical course was relapsing, and all three dogs responded
in a mature dog,' and spinal muscular atrophy, an variably to corticosteroid therapy. Numerous positive sharp
waves and fibrillation potentials were detected in appendic-
abiotrophy that occurs in young Rottweiler puppies ular muscles by electromyographic testing, primarily in mus-
around 4-6 weeks of age.47.48 In this article, we report cles distal to the elbow and stifle. Few abnormal potentials
another neurologic disorder in this breed, a progressive were noted in proximal limb and paraspinal muscles. Motor
degenerative polyneuropathy with a distal axonal dis- nerve conduction velocities were reduced- I2 m/second, 39
tribution, that has been found to date only in mature m/second, and 40 m/second, respectively, as compared with
Rottweilers. normal values of 50-60 m/second4-in three of eight dogs
tested. Sensory nerve conduction velocity was reduced in one
dog tested-5 m/second as compared with normal values of
Materials and Methods > 60 m / s e c ~ n d Hematology,
.~ blood chemistries, and spinal
Eight mature Rottweilers (six male and two female) be- radiography/myelography were normal in all dogs tested. Ce-
tween ages 1.5 and 4 years were studied for progressive neu- rebrospinal fluid protein was marginally elevated in one of
rologic disease. There was no historic evidence of any dog four dogs tested. Pleiocytosis was not observed. With the
being exposed to a toxic substance. Clinical signs were char- exception of one dog that was serologically positive for valley
acterized by paraparesis that progressed to tetraparesis, spi- fever and Ehrlichia canis ( 1 : 80), tests for immunologic (an-
nal hyporeflexia and hypotonia, and appendicular muscle tinuclear antibodies, rheumatoid factor, lupus erythematosus
atrophy in distal limb muscles. Dogs typically developed a cells, antiglobulin [Coombs']), endocrine (diabetes, hypothy-
plantigrade stance associated with a crouched, waddling gait. roidism, hyperadrenocorticism), toxicity (lead, cholinester-
Cranial nerve function was normal. Sensory deficits were not ase levels). and infectious (Rocky Mountain spotted fever,
3 16
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borreliosis, ehrlichiosis, canine distemper) disease were neg-
ative.8
Muscle samples from biceps femoris, lateral head of the
gastrocnemius, superficial digital flexor, or cranial tibial mus-
cle, approximately 2 x 2 x 2 cm, were obtained without the
use of clamps from eight Rottweiler dogs under general an-
esthesia, placed in glass or plastic bottles, and cooled using
gel freeze packs. At the same time, fascicular segments of
nerves (either common peroneal, ulnar, tibial, superficial ra-
dial, saphenous, or proximal sciatic) were removed, gently
stretched on wooden tongue depressors with pins, and fixed
in a mixture of 4% formalin/l% glutaraldehyde, 2.5% glu-
taraldehyde in phosphate buffer, or 10% neutral buffered
formalin. Muscle and nerve biopsy samples were mailed via
overnight delivery to the Neuromuscular Laboratory, Scott-
Ritchey Research Center, Auburn University, for routine Fig. 1. Skeletal muscle; dog No. 1. Marked fiber size
processing. Upon receipt at the Neuromuscular Laboratory, variation associated with atrophic and hypertrophic fibers.
muscle samples were oriented in transverse and longitudinal HE. Bar = 50 fim.
planes and frozen in isopentane, precooled in liquid nitrogen.
Samples were stored in airtight plastic bottles at - 80 C. Serial
sections were cut at 8 l m and stained for routine morphologic Dorsal and ventral nerve roots were sampled from lumbar
and histochemical cord segments and processed for single fiber teasing, semithin
Nerves were divided into halves and washed in phosphate sections, and ultrathin sections.
buffer (pH 7.3) at 4 C overnight. One half was postfixed in For quantitative studies, transverse sections of ulnar, ra-
1Yo osmium tetroxide for 6-8 hours, placed in 66% glycerin dial, proximal sciatic, and distal tibial nerves from the nec-
for 24 hours, and stored in 100% glycerin for single teased- ropsied dog, together with samples from age-matched control
fiber preparations as previously described. l o The second half dogs, were projected onto a monitor using a computerized
of each nerve was further fixed in 1% osmium tetroxide for video-display image analysis system (Optomax semiauto-
1 hour, washed in phosphate buffer, transferred through grad- matic image analysis system, Optomax, Hollis, NH). The
ed ethanol solutions, and then processed for embedding in mean external diameters of the axons that were myelinated
Epon plastic medium. Semithin sections (1-2 pm) were cut were determined from a random field fiber count of approx-
transversely and stained with paraphenylene diamine31 or imately 1,500 for each nerve sample. Random counts were
toluidine blue.5 Silver to gray ultrathin sections of nerves made from four quadrants of each section to avoid the pos-
were cut, stained with uranyl acetate and lead citrate, and sibility of inadvertently over- or undersampling large or small
examined with a Philips 301 electron microscope. Nerve fibers. All measurements were made under oil objective at a
samples previously obtained from normal dogs of compa- final magnification of 2,940 x . Sections were acceptable for
rable ageIoJ2were similarly processed. measurement only when the majority of fibers were circular
Approximately 100 single fibers from each nerve sample in shape. The diameter of the lesser axis was used on oval
were teased at random from all fascicles, without preselection fibers. Triangular fibers were measured across their base.
for size or abnormality, and were histologically classified Crenaled fibers were not measured.
according to the system of Dyck:28A = teased fiber of normal
appearance; B = normal fiber with excessive rnyelin irregu- Results
larity, wrinkling, or folding; C = teased fiber with single or Morphology
multiple regions of nodal lengthening or lack of internodal
myelin (as evaluated by use of high-dry light objective); D Skeletal muscle changes were characterized by
= single or multiple C and F abnormalities combined; E = marked fiber size variation associated with atrophic
teased fiber with linear rows of myelin ovoids and balls; F and hypertrophic fibers (Fig. 1). Atrophic fibers were
= teased fiber without site(s) of segmental demyelination but angular and sometimes formed small and large groups
with excessive variability of myelin thickness between in- in a disseminated random distribution. Most of the
ternodes (thickness of myelin of the internodes with the thin- atrophic fibers were type 11, whereas hypertrophic fi-
nest myelin is < 50% of that of the internode with the thickest bers were type I or type 11. Fiber type grouping was
myelin); and G = teased fiber without site(s) of segmental not seen in any sample. In some areas, there was a
demyelination but with excessive variability of myelin thick-
relative increase in perimysial and sometimes endo-
ness within internodes to form globules or “sausages.” Fibers
with segmental demyelination and remyelination were rep- mysial connective tissue. Depletion of myelinated fi-
resented by the graded lesions, C , D, F, and G. Fibers un- bers was noted in some intramuscular nerves. Muscle
dergoing axonal degeneration were represented by E. changes were more prominent in distal muscles (such
Only one dog was available for necropsy. Samples from as lateral head of gastrocnemius and cranial tibial mus-
lumbar spinal cord and brain were fixed in 10% neutral buf- cle) than in more proximal muscles (such as biceps
fered formol solution and processed for paraffin embedding, femoris). There was no evidence of necrosis, phago-
Downloaded from vet.sagepub.com by guest on May 8, 2015318 Braund, Toivio-Kinnucan. Vallat. Mehta, and Levesque Vet Pathol 31:3, 1994
Fig. 2. Sciatic nerve; control dog. Normal distribution of Fig. 3. Sciatic nerve; dog No. 5. Loss of myelinated nerve
small- and large-caliber fibers. Paraphenylene diamine. Bar fibers and several fibers with inappropriately thin myelin
= 25 bm. sheaths (arrows). Paraphenylene diamine. Bar = 25 pm.
cytosis, or inflammation in any muscle sample ex- with macrophages containing myelin debris within the
amined. Schwann cell cytoplasm or in the endoneurium in close
In cross-sectional preparations of nerves from af- proximity to the Schwann cell (Fig. 7). Additionally,
fected animals, changes were more severe in distal parts there was increased endoneurial collagen, occasional
of nerves than in more proximal regions and nerve fibers with excessively thick myelin sheaths and small
roots (Figs. 2-4). Abnormal findings included axonal axonal compartments (Fig. S), many axons with my-
necrosis, loss of myelinated nerve fibers (especially those elinlike profiles (Fig. 9), and numerous Biingner bands
of larger caliber), occasional macrophage infiltration, (Fig. 10). Many axons had a watery appearance with
and variable numbers of fibers with inappropriately loss of neurofilaments and microtubules. There was no
thin myelin sheaths. Inflammation was not observed evidence of neurofilamentous accumulation. Regen-
in any nerve. The incidence of abnormalities in teased erating clusters were uncommon, and onion bulb for-
fibers from different nerves of affected dogs is given in mation, indicative of repeated demyelination and re-
Table 1. The most dominant abnormality in all dogs , ~ ~ rare (Fig. 11). In several nerves,
m y e l i n a t i ~ n was
was axonal necrosis, characterized by linear rows of degenerating endoneurial fibroblasts were seen with
myelin ovoids and balls (graded lesion E) (Fig. 5). In dark pyknotic nuclei, disrupted plasma membranes,
several dogs, demyelination (graded lesion C) and re- and organelles lying free in the endoneurium. In one
myelination (graded lesion FJ or both involving the dog, the perineurium was thickened and contained nu-
same fiber (graded lesion D) were also observed. These merous cells filled with lipidlike vacuoles. Endoneurial
changes were more apparent in dogs with a chronic capillaries appeared normal. Lesions were commonly
clinical course. In one such dog, demyelination and noticed in unmyelinated fibers from affected dogs, but
remyelination were common in dorsal and ventral nerve not in those of controls. These lesions were character-
roots (Table 1). ized by increased numbers of Schwann cell profiles and
Ultrastructural examination of motor nerves re- loss of axons in Schwann cell subunits (Fig. 12).
vealed occasional fibers with myelinoaxonal necrosis Schwann cell bands devoid of axons, enclosed by a
(Fig. 6) and variable numbers of demyelinated fibers continuous basement membrane with redundant loops,
Downloaded from vet.sagepub.com by guest on May 8, 2015Vet Pathol 3 I :3, I994 Distal Sensorimotor Polyneuropathy in Rottweilers 319
Fig. 5. Teased nerve fiber panel; dog No. 4. Osmium
tetroxide. Bars = 25 pm. Fig. 5a. Normal myelinated fiber
with node of Ranvier (arrow).Fig. 5b. Paranodal demyelin-
ation. Fig. 5c. Linear rows of myelin ovoids and balls. Fig.
5d. Intercalated internode (arrows = nodes of Ranvier).
medium (5.5-8 pm) and large (8.5-12.5 pm) fibers.
Similar findings were noted in radial nerve. Loss of
medium- and large-caliber fibers was noted also in
distal tibial nerve as compared with more proximal
sciatic nerve segments in an affected dog, and the peak
of the histogram in the distal nerve was situated be-
tween 2 and 3 pm (Fig. 14). Mean fiber diameters for
proximal and distal segments were 4.95 f 2.75 pm
and 2.41 t 0.71 pm, respectively.
Fig. 4. Distal tibial nerve; dog No. 5. Focal axonal de-
generation (arrow)and pronounced loss of medium- and large- Discussion
caliber fibers. Paraphenylene diamine. Bar = 25 pm. This Rottweiler polyneuropathy appears to be a dis-
tinct breed-related clinical entity. Clinical signs of mus-
cle atrophy, hyporeflexia, and hypotonia are indicative
were common. Many axons of unmyelinated fibers also of a neuropathic syndrome6and therefore are clinically
had a watery appearance and contained sparse num- distinct from neuroaxonal dystrophy and leukoenceph-
bers of neurofilaments and microtubules. Collagen alomyelopathy described in this breed.20,21,32,34,49.55 Spi-
pockets were often seen. nal muscular atrophy is an abiotrophic disorder af-
Similar but less severe changes were observed in fecting ventral horn cells in the spinal cord of young
sensory nerves (such as superficial radial and saphe- Rottweiler puppies about 5-6 weeks of age.47.48 Af-
nous). In one dog with a chronic clinical course, fine fected puppies show signs of megaesophagus, progres-
granular deposits were observed in several nerves. sive ataxia, and pelvic limb weakness. In contrast with
These deposits were sometimes membrane bound and the Rottweilers in the present study, lesions include
were noted within Schwann cell cytoplasm of myelin- central chromatolysis and swelling of the perikarya in
ated and unmyelinated fibers, free in the endoneurium, many large motor neurons in the ventral gray matter
and within capillary walls (Fig. 7). These deposits may of the spinal cord and various brain stem nuclei. Chro-
represent a fixation artifact. matolytic neurons have excess numbers of neurofila-
No abnormalities were observed in brain or lumbar ments and an increase in and enlargement of Golgi
spinal cord segments from the one affected Rottweiler complexes. This Rottweiler polyneuropathy also dif-
available for necropsy. fers from the chronic polyneuritis reported in a 2-year-
old Rottweiler.' Although the electromyogram initially
Morphometry revealed fibrillation potentials bilaterally in muscles
The mean fiber diameters of myelinated fibers in below the elbows and stifles in this dog with polyneu-
ulnar nerves from control and affected dogs were 5.62 ritis, weakness and atrophy developed in proximal limb
f 2.58 pm and 3.94 k 1.78 pm, respectively. The muscles, lumbar epaxial muscles, and muscles of the
histographic distribution of the control nerve was bi- head. Furthermore, initial clinical signs and muscle
modal. In contrast, that of the affected ulnar nerve was atrophy were more pronounced in thoracic limbs. Fi-
unimodal (Fig. 13), with conspicuous reduction/loss of nally, pathologic changes were quite different in this
Downloaded from vet.sagepub.com by guest on May 8, 2015320 Braund, Toivio-Kinnucan. Vallat, Mehta, and Levesque Vet Pathol 31:3. 1994
dog with polyneuritis, being characterized by inflam-
matory cell infiltrates of peripheral nerves (including
dorsal and ventral roots) and cranial nerves, demy-
elination, and focal meningitis and gliosis in the brain
at the entrance/exit points of cranial nerves.
The pathologic changes in the Rottweilers were char-
acterized by neurogenic muscle atrophy secondary to
a peripheral neuropathy that was dominated by axonal
necrosis. The changes were most severe in the motor
nerves, with less severe involvement of sensory nerves.
Presence of numerous bands of Biingner or denervated
Schwann cells, indicative of axonal loss in myelinated
fibers, together with many myelinated fibers showing
depletion of axonal contents, increased amounts of
electron-dense clumping, and watery appearance, are
hallmarks of axonal n e c r o s i ~ Membranous
. ~ ~ ~ ~ ~ ~ma-
~~
terial with myelinlike appearance seen in affected ax-
ons may suggest early axonal degeneration. Similar
axonal pathology has been seen in a variety of neu-
ropathies in animals and humans (personal observa-
tions) and has been reported recently in experimental
acrylamide intoxication in rats.35Ovoids contained a
mixture of disintegrating myelin segments and degen-
erated axonal component^.^^ There was conspicuous
involvement of unmyelinated fibers, as suggested by
Fig. 6 . Electron micrograph. Nerve; dog No. 1. Myeli- the presence of collagen pockets, increased numbers of
noaxonal necrosis with vesiculomembranous accumulations. profiles in Schwann cell subunits, and increased num-
Bar = 1 urn. ber of subunits devoid of ax on^,^^.^^.^^ as compared with
control nerves.
Table 1. Percentage of abnormal teased nerve fibers from Rottweiler dogs with distal polyneuropathy.
Histologic Classificationt Total Percentage
Abnormal Fibers
Dog Sex Age Nerve*
No. (years) Affected Control
C D E F
Dogs Dogs
1 M 2 CPN 0 0 45 0 0 45 0
Ulnar 3 0 24 0 0 27 0
2 F CPN, 3 0 16 0 0 19 0-3
3 M Tibial I 0 7 0 1 9 0-3
4 F Tibial 13 2 33 3 0 51 0-3
5 M Tibialt 0 0 50 2 0 52 0-3
Sup Radials 2 0 14 0 0 16 0-3
Tibia14 14 10 46 0 0 70 0-3
Dorsal root§ 0 0 0 24 0 24 0-3
Ventral roots 2 0 0 10 1 13 0-3
6 M 1.5 Tibial 0 0 50 0 0 50 0
7 M 4 CPN II 0 0 6 0 0 6 0-3
Sciatic# 8 20 4 32 2 66 0-3
8 M 3 Sciatic 5 0 7 2 5 19 0-3
* CPN = common peroneal nerve; Sup Radial = superficial radial nerve.
t C = single or multiple regions of nodal lengthening or internodal myelin absence; D = single or multiple C and F abnormalities
combined E = linear rows of myelin ovoids and balls; F = 50% or more difference in myelin thickness between internodes; G = thickening
or reduplication of myelin to form globules within internodes.”
#First biopsy (1 1/30/89).
8 Necropsy (5/24/90).
I( First biopsy (4/13/90).
# Second biopsy (8/14/90)
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322 Braund, Toivio-Kinnucan, Vallat, Mehta, and Levesque Vet Pathol 31:3. 1994
Fig. 8. Electron micrograph. Nerve; dog No. 4. Fiber with Fig. 9. Electron micrograph. Nerve; dog No. 3. Axon
excessively thick myelin sheath and small axonal cornpart- with myelinlike profiles (arrows). Bar = 1 pm.
ment. Bar = 1 pm.
Fig. 10. Electron micrograph. Nerve; dog No. 4.Bungner Fig. 11. Electron micrograph. Nerve; dog No. 6. Onion
band. Bar = 0.5 pm. bulb formation. Bar = 1 prn.
Downloaded from vet.sagepub.com by guest on May 8, 2015Vet Pathol 31:3, 1994 Distal Sensorimotor Polyneuropathy in Rottweilers 323
with vesiculomembranous accumulations were seen in
nerves from the Rottweilers, there was no evidence of
neurofilamentous accumulations as seen in CAN or in
acrylamide and hexacarbon toxicity,24,36,46,52 no intra-
axonal accumulations of proliferating endoplasmic re-
ticulum as seen in organophosphate n e ~ r o p a t h yand ,~~
no tubulovesicular accumulation^^^ or accumulations
of mitochondria and dense lamellar bodies associated
with axonal o ~ t p o u c h i n g sas
~ ~described in nerves of
horses with idiopathic laryngeal hemiplegia. Further-
more, there was no sign of the vesiculotubular profiles
in unmyelinated fibers reported in nerves from long-
haired Dachshunds with the distal sensory neuropa-
thy.26From these studies, a number of pathogenetic
mechanisms have been suggested to explain the dying-
back abnormalities: primary toxicity of the nerve cell
body,46Schwann cell a b n o r m a l i t i e ~primary
,~~ axonal
changes,soand disrupted axonal f l o ~ . ’ ~ , ~ ~
The apparent depletion of large-caliber myelinated
fibers in the Rottweilers, as seen by light microscopic
and morphometric studies, is consistent with the dy-
ing-back concept.I9 A similar loss of larger myelinated
fibers has been reported from morphometric studies
in dogs with distal symmetrical polyne~ropathy~ and
distal sensory neuropathy26and in horses with idio-
Fig. 12. Electron micrograph. Nerve; dog No. 6. Un- pathic laryngeal hemiplegia.13,25 Nerve fiber diameter
myelinated fibers are flattened and there is loss of axons. Bar is reportedly more important than axonal length in
= 0.5 um. determining differential vulnerability of peripheral
nerve fiber degeneration in experimental dying-back
diseases.53
The Rottweiler polyneuropathy has clinical, electro-
n = 1500 flbers (Contrd), 648 Qottweiler)
Mean fiber diameter = 5.62 pm (Contrd), 3.94 pm (Rottweiler)
0.5 1 1.5 1 l.5 3 3.5 4 4.5 5 5.5 6 6.5 7 13 1 1.5 9 9.5 LO 10311 11.511 113 13
DLmctv
Fig. 13. Ulnar nerve; dog No. 5. Bimodal histographic distribution of control nerve. Unimodal distribution of affected
ulnar nerve.
Downloaded from vet.sagepub.com by guest on May 8, 2015324 Braund, Toivio-Kinnucan. Vallat. Mehta, a n d Levesque Vet Pathol 31:3, 1994
300
n = 828 fibers (Sciatic), 972 (Distal tibial)
Mean fiber diameter = 4.95 pm (Sdatic),
2 4 1 p n (Distal tibtl)
200
x
L
5
z
Sdatk
Dfstnltibid
100
0
0.1 1 1 3 1 U 3 3.1 4 4 3 1 S.S 6 6 3 'I 7 3 8 8 3 9 9.S I0 10.S11 l l . S I 2 1 1 3 1 3
Diameter
Fig. 14. Sciatic and tibial nerves; dog No. 5. Histogram of loss of medium- and large-caliber fibers in distal tibial nerve
as compared with more proximal sciatic nerve segments from an affected dog.
diagnostic, and pathologic (quantitative and qualita- where there is degeneration of the distal intramuscular
tive) similarities to distal symmetrical polyneuropathy axons and from which the majority of dogs recover.37
that has been described in large-breed dogs, including The chronic, relapsing course noted in three dogs and
Great D a n e ~ , ~Irish
. ~ * Setter crosses,22St. Bernards, the variable response to corticosteroids suggests a pos-
Newfoundlands, and Chesapeake Bay Retrievers (K. sible immunologic pathogenesis, although demyelin-
G. Braund, unpublished data). In the Rottweilers, dif- ation rather than axonal degeneration is more typically
ferences included the relapsing clinical course in some the dominant lesion in such disorders.54The nature of
dogs and more pronounced involvement of unmyelin- the granular deposits noted in several nerves of one
ated fibers. dog is uncertain; however, they appear to be structur-
The cause of the disease was not determined. A toxic ally different from immunoglobulin deposits and am-
cause was considered; however, based on absence of y10id.~~
both historic and laboratory evidence of exposure to To determine if this Rottweiler polyneuropathy rep-
a toxin and lack of characteristic axonal pathology nor- resents a central-peripheral distal a x ~ n o p a t h y ' ~ . ~ ~ , ~ ~ . ~
mally seen with organophosphates, acrylamide, or tox- characterized by additional presence of axonal degen-
ic hexacarbons, toxicity was considered unlikely. There eration in selected pathways of the central nervous
was n o evidence of nutritional disorders, uremia, or system (e.g., spinocerebellar tracts and dorsal columns
diabetes, which have been associated with distal sym- in upper cervical cord segments, rubrospinal and cor-
metrical polyneuropathy in human^,^ and laboratory ticospinal tracts in lumbosacral cord segments), further
tests for immunologic, infectious, and endocrine dis- studies of spinal cord from affected animals are needed.
ease were negative. Apart from GAN in German She- Spinal cord (lumbar segments) was available from only
phard Dogs, sensory neuropathy in long-haired Dachs- one dog; however, no changes were observed. To date,
hunds, idiopathic laryngeal hemiplegia in horses, and central-peripheral distal axonopathy has been reported
distal symmetrical polyneuropathy in large-breed dogs, in several distal axonopathies of animals: in horses
a distal dying-back form of neuropathy also has been with idiopathic laryngeal hemiplegia,16J7in Birman
reported in a litter of Birman in horses with in German Shepherd Dogs with GAN,24.36 and
stringhalt,'* and in dogs with diabetic neuropathy,12.4i in long-haired Dachshunds with sensory neuropathy.26
and it is believed to be the mechanism underlying la- This Rottweiler neuropathy has morphologic and
ryngeal paralysis with associated polyneuropathy in morphometric similarities to hereditary motor and
dogs, especially young Dalmatians. I I The Rottweiler sensory neuropathy (HMSN) type I1 in humans, a neu-
condition is clinically, electrodiagnostically, and path- ronal type of peroneal muscular a t r ~ p h y .Affected
~~,~~
ologically different from distal denervating disease patients have normal or slightly reduced nerve con-
Downloaded from vet.sagepub.com by guest on May 8, 2015Vet Pathol 3l:3, 1994 Distal Sensorimotor Polyneuropathy in Rottweilers 325
duction velocities. Morphologically, HMSN type I1 is Neurology, ed. Oliver JE, Hoerlein BF, and Mayhew IG,
characterized by decreased numbers of myelinated fi- pp. 145-166. WB Saunders, Philadelphia, PA, 1987
bers, primarily large-diameter fibers (> 8 pm) as a re- 5 Bradley WG: Disorders of Peripheral Nerves, pp. 129-
sult of axonal degeneration, with a shift to smaller 309. Blackwell Scientific, Oxford, England, 1974
6 Braund KG: Clinical Syndromes in Veterinary Neurol-
diameters in histograms, which typically have an uni-
ogy, pp. 40-43. Williams & Wilkins, Baltimore, MD,
modal peak in the 2-3 pm range. There is variable 1986
demyelination, especially paranodal, but with minimal 7 Braund KG, Hoff EJ, Richardson KEY: Histochemical
onion bulb f ~ r m a t i o n . ~Changes
~ , ~ ~ .are
~ ~more severe identification of fiber types in canine skeletal muscle. Am
in distal portions of motor and sensory nerves.29.33.44 J Vet Res 39:561-565, 1978
Autosomal dominant and autosomal recessive modes 8 Braund KG, Levesque DC, Shores A, Northington JW,
of inheritance have been d e ~ c r i b e d .As
~ ~was
. ~ ~noted Palmer D: Distal polyneuropathy in mature Rottweiler
in the Rottweilers, axonal regeneration is rare in re- dogs. J Vet Intern Med 5:147, 1991 [Abstract]
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Braund KG, McGuire JA, Lincoln CE: Age-related
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The possible role of genetic factors in the Rottweiler 11 Braund KG, Steinberg HS, Shores A, Steiss JE, Mehta
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grees for the affected dogs were unavailable. Giant ax- ysis in immature and mature dogs: one manifestation of
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as autosomal recessive trait^.^^,^^,^^,^^ A congenital or diabetes mellitus in the dog. Acta Neuropathol 57:263-
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might be another useful animal model for the study of 14 Cahill JI, Goulden BE: Equine laryngeal hemiplegia. 11.
distal polyneuropathies in humans and of HMSN type An electron microscopic study of peripheral nerve. NZ
I1 in particular. Vet J 34:170-175, 1986
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A teased fiber study of peripheral nerves. NZ Vet J 34:
We thank the following clinicians for providing tissue sam- 18 1-1 85, 1986
ples: Dr. A. Shores, Michigan State University, East Lansing, 16 Cahill JI, Goulden BE: Equine laryngeal hemiplegia. V.
Michigan; Dr. J. Northington, Metropolitan Veterinary As- Central nervous system pathology. NZ Vet J 34: 19 1-1 93,
sociates, Valley Forge, Pennsylvania; Dr. D. Palmer, Texas 1986
A&M University, College Station, Texas. We also thank Dr. 17 Cahill JI, Goulden BE: Further evidence for a central
S. Wheeler, North Carolina State University, for providing nervous system component in equine laryngeal hemi-
brain and lumbar spinal cord from one affected dog. This plegia. NZ Vet J 37:89-90, 1989
study was supported by funds from the Neuromuscular Di- 18 Cahill JI, Goulden BE, Jolly RD: Stringhalt in horses:
agnostic Laboratory, Scott-Ritchey Research Center, College a distal axonopathy. Neuropathol Appl Neurobiol 12:
of Veterinary Medicine, Auburn University, Auburn, Ala- 459-475, 1986
bama. 19 Cavanagh JB: The significance of the “dying back” pro-
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Request reprints from Dr. K. G. Braund, Neuromuscular Laboratory, Scott-Ritchey Research Center, Auburn University,
College of Veterinary Medicine, Auburn, AL 36849-5525 (USA).
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