REVIEW

INTRODUCTION

Neurological
manifestations
01 canine
distemper virus
infect&
F

A. Tipold, M. Vandevelde and A. Jaggy

Institute of Animal Neurology, University of Berne, Bremgartenstrasse 109a, 3001 Bern, Switzerland

[ournal ofSmol1Animul Pructice (1992) 33,466-470

Canine distemper was first reported in Europe

in 1761 (Fankhauser 1982). For a long time
distemper was a major cause of neurological
disease in dogs. Although widespread use of
vaccination since the 1950s and 1960s markedly
reduced the incidence of distemper, outbreaks
still occur and neurological manifestations of
distemper are by no means rare. Canine distemper is a highly contagious disease caused by a
morbillivirus that is closely related to the
measles and rinderpest viruses (Appel and
Gillespie 1972). Canine distemper virus (CDV)
can infect a wide range of carnivores, including
members of the Canidae, Procyonidae and
Mustelidae (Appel and Gillespie 1972). Dogs
with acute systemic CDV infection shed the virus
in their faeces, saliva, urine and conjunctival and
nasal exudates. The virus enters the host usually
by way of an aerosol infection (Appel and others
1981).

ABSTRACT
~~~

Canine distemper virus causes a multisystemic

disease in dogs often with severe neurological
signs. These signs are the result of viral replication in neurons and glial cells leading to grey
matter lesions and demyelination. Inflammation
leads to further destruction of the tissue. As
extraneural signs are often lacking and only one
localisation may be found on neurological examination, distemper may be 'difficult to diagnose.
Myoclonus is almost pathognomonic for this disease but occurs in less than half of the cases. The
inflammation of the central nervous system that
occurs during the chronic stage of the disease can
be detected on examination of the cerebrospinal
fluid, in particular by determination of the IgG
index. Viral antigen can be demonstrated in cerebrospinal fluid cells by fluorescent antibody
techniques. The prognosis of nervous distemper
is generally poor although dogs can recover from
this disease. Treatment is largely supportive and
symptomatic. The importance of regular vaccination is stressed.

Virus replication starts in the lymphoid tissues. When lymphatic tissue infection becomes
widespread, viraemia develops and an initial rise
in body temperature and leucopenia is observed.
Viral antigen can be found in buffy coat preparations during this time. Ten to 14 days after inoculation the virus invades various epithelial tissues
and the central nervous system. CDV enters the
brain parenchyma through the cerebrospinal
fluid pathways (Higgins and others 1982) or
crosses the blood-brain barrier by way of infected
lymphoid cells (Summers and others 1979). In
the central nervous system it replicates in neurons and in glial cells, resulting in grey matter
and white matter lesions with demyelination. In
many cases demyelination is the most important
finding.
The initial lesions in the white matter are not
inflammatory and are the result of viral replication in glial cells (Vandevelde and others 1985).
These lesions are characterised by demyelination
and occur in predilection sites such as the cerebellum, optic system and spinal cord. A chronic
course can result from a late or insufficient
immune response against CDV (Krakowka and
others 1975, Appel and others 1982). Inflammation in the demyelinating lesions during
the chronic disease may lead to further damage
of the white matter (Vandevelde and others
1982).

The virulence of the viral strain, the age and

the immunocompetence of the dog determine the
course and outcome of the disease. Strain variations have been studied in experimental distemper, in which the Snyder Hill strain caused a
polioencephalomyelitis and the A 75-17 and
R 252 strains of CDV a demyelinating disease

Neurological manifestations of canine distemper virus infection

(Summers and others 1984). It is uncertain

whether Snyder Hill CDV-like viruses occur in
nature: the current authors found no evidence
that a CDV-induced polioencephalitis, like the
Snyder Hill-induced disease, occurs spontaneously. In the acute stage of the infection a
severe immunosuppressive effect of CDV is
observed (Krakowka and others 1980). Without
an effective antiviral immune response infected
dogs will develop a rapidly progressive disease
and die. Dogs which are able to respond
immunologically early to CDV infection will
recover with little or no clinical signs. Dogs with
a delayed immune response tend to develop a
chronic neurological disease (Appel and others
1982). The inflammation is often associated with
worsening of the tissue damage and progression
of the neurological signs. At this stage of the disease there is intrathecal production of antibodies
by infiltrating lymphocytes. These antibodies are
directed against CDV as well as against myelin
antigens, mainly myelin basic protein (Vandevelde and others 1986). It has been shown in
vitro that antiviral antibodies can stimulate
macrophages with secretion of free radicals of
oxygen (Griot and others 1989). In vitro it has
been shown that these radicals are highly toxic to
oligodendrocytes, the myelin producing cells
(Griot and others 1990). This mechanism could
be responsible for the severe tissue damage seen
in chronic demyelinating lesions in distemper.
CDV is able to persist in the central nervous
system despite the presence of an intrathecal
immune response providing a continuous source
of viral antigen to maintain such tissue damaging
reactions.

CLINICAL SIGNS
~

Despite the relatively large experimental and

neuropathological literature on nervous distemper there are only a few indepth studies on the
clinical neurology of distemper. The present
authors have studied about 100 well documented
cases of nervous distemper during the past few
years. Much of what follows is based on this
experience.
According to most clinical textbooks CDVinfected dogs develop a systemic disease, including fever, gastrointestinal and respiratory signs,
followed by neurological disease two or three
weeks later. However, such classical presentation is not the rule. It has been claimed in various publications that neurological signs in
distemper may occur much later (months or
years) after the systemic infection as a post
infectious encephalitis. However, there is
neither experimental evidence nor any conclu-

sive clinicopathological observations in the

spontaneous disease to support this notion.
According to the owners of the animals in this
series, systemic signs were often very mild or
absent. Only in a third of the present cases was
extraneural involvement such as gastrointestinal
or respiratory signs, fever and conjunctivitis
noted by the owner, either preceding the neurological signs or occurring simultaneously. On
clinical examination two-thirds of the animals
were presented with (often mild) extraneural
signs, including conjunctivitis and fever, respiratory signs, gastrointestinal involvement, tonsillitis, cachexia and hyperkeratosis of the footpads
or of the nose. In a third of the dogs no extraneural signs were found at all.
There was neither a breed nor sex predisposition in this material and none has been reported.
Although a little more than a half of the cases
were younger than one year of age (about a third
less than four months of age), distemper was
often seen in adult dogs.
The duration of the neurological disease varied
from a few days to more than one month. Consistent with the literature, which shows that distemper is generally a monophasic disease (Greene
and Appel 1990), only one of the present dogs
had a chronic relapsing course.
Neurological signs vary widely in canine distemper. The signs should reflect the distribution
of the virus and lesions in the central nervous
system. In the experience of the present authors,
a clinicopathological correlation is often lacking
in neurological distemper. On histological examination the lesions are mostly multifocal, but
often only one localisation is found on clinical
examination. For example, in about a third of
these cases spinal cord signs with paresis and
ataxia of the limbs were the only neurological
findings. Other common signs included central
vestibular disease (head tilt, nystagmus, tendency to fall, cranial nerve and conscious proprioceptive deficits) and cerebellar disease (ataxia
with hypermetria and head bobbing) and generalised or partial seizures. Uni- or bilateral blindness, sometimes with dilated pupils, caused by
the frequent involvement of the optic nerves and
tracts is present. In some animals, mild swelling
of the optic disc or a retinitis may be found on
fundic examination. Generalised muscle atrophy
is rare as is a clinical presentation of a focal cortical lesion.
Myoclonus, that is, rhythmic jerking of single
muscles or muscle groups, is a common sign in
canine distemper and was found in 40 per cent of
these cases, involving mostly the muscles of the
limbs, the head and rarely the trunk. Although
myoclonus is often considered to be a pathognomonic sign in distemper, it is also observed
in other inflammatory diseases of the central ner467

A . TIPOLD AND OTHERS

vous system in dogs. The pathogenesis of

myoclonus remains uncertain; experimental
studies suggest that focal spinal cord lesions may
be responsible. Another possibility is that a basal
nucleus lesion may initiate this sign and establish a pacemaker in the spinal cord or brainstem, which maintains the involuntary muscle
activity (DeLahunta 1983).
It has been reported before that distemper can
occur together with other infections in the central nervous system (Greene and Appel 1990).
The massive immunosuppression caused by CDV
can lead to activation of a latent protozoal infection. In six cases in this series a combined infection of distemper with Toxoplasma gondii or
Neospora caninum was found. Such animals had
lower motor neuron signs, electromyographic
changes including fibrillation potentials and positive sharp waves, slowed nerve conduction
velocity and severe myositis as detected on muscle biopsies (Wolf and others 1991).

LABORATORY FINDINGS
A frequent haematological finding is lymphopenia, sometimes combined with leucopenia
or leucocytosis with left shift, anaemia, monocytosis and rarely thrombocytopenia (Greene and
Appel 1990). Lymphopenia, a sign of immunosuppression in CDV infection, is also combined
with a decrease of lymphocyte responsiveness to
lectin stimulation (Cerruti-Sola and others 1983).
Serum biochemical findings including electrophoresis are non-specific and rarely useful for
diagnosis in this disease.
Examination of the cerebrospinal fluid can be a
very useful diagnostic procedure in distemper.
However, during the acute demyelinating stage of
the disease, inflammatory reactions are lacking
and protein and cell content of the cerebrospinal
fluid may be normal (Vandevelde and others
1986). In the chronic stage of the disease, inflammation occurs with invasion of mononuclear
cells in the lesions and the cerebrospinal fluid. In
such cases pleocytosis is frequently but not
always found (Bichsel and others 1984).
Many of the invaded cells are immunoglobulin-producing lymphocytes. By measuring the
IgG content in cerebrospinal fluid and serum and
using the corresponding albumin values as a reference, the so called IgG index can be determined (Bichsel and others 1984, Tipold and
others 1992). The IgG index is elevated in most
cases with inflammatory distemper, even in
those cases in which no significant pleocytosis
can be found. However, the index is normal in
most dogs with acute non-inflammatory distemper. The demonstration of an elevated IgG index
468

is very helpful to detect the presence of inflammation of the central nervous system but is not
specific for distemper (Tipold and others 1992).

DIAGNOSIS
A clinical diagnosis of distemper is often difficult when the typical presentation of the disease
with neurological signs developing after systemic
symptoms is lacking. Likewise, myoclonus,
which is highly suggestive of nervous distemper,
is lacking in more than half of the cases. When
multifocal neurological signs are found, an
inflammatory disease of the central nervous systtem is suspected and can be confirmed by cerebrospinal fluid examination.
CDV infection should be considered in the differential diagnosis in such cases. As described
above, frequently only one localisation is found.
Such cases of distemper with focal signs and in
which other typical findings such as extraneural
signs or myoclonus are lacking, are a diagnostic
challenge for the veterinary surgeon. Other focal
lesions have to be excluded by a variety of imaging techniques. Careful cerebrospinal fluid examination in such animals may reveal the presence
of inflammation suggesting the possibility of
CDV infection.
A final diagnosis is based on the demonstration of viral antigens in scrapings and body
fluids such as conjunctival smears, tracheal
washing, urine sediment and cerebrospinal fluid
cells. Viral antigen can be hard to find in the
extraneural tissues in cases with neurological
distemper without systemic signs. Viral antigen
can be detected in cerebrospinal fluid cells with
an indirect fluorescent antibody test using antiCDV antibodies. For this technique the cerebrospinal fluid cells have to be concentrated first
by sedimentation or centrifugation (Vandevelde
and Spano 1977). Frequently, only small numbers of cells can be obtained. The demonstration
of anti-CDV antibodies in serum is of limited
diagnostic value. Comparing serum antibody
titres with intrathecally produced anti-CDV IgG
may help diagnostically, however, severely
immunosuppressed animals may not have any
detectable antibody at all.

PROGNOSIS
The prognosis of CDV-infection with neurological signs is generally guarded, especially in
cases with severe immunosuppression and rapidly progressing clinical signs. Seizures in CDVinfection are an unfavourable prognostic sign
because they are generally difficult to control

Neurological manifestations of canine distemper virus infection

with anticonvulsants. Dogs in which the immune

response recovers in the early stage of the disease
have a better prognosis. When the neurological
signs are not debilitating, the animal need not be
euthanased as soon as a diagnosis of distemper is
established. Because dogs have a chance to
recover from the disease, supportive treatment is
recommended for one or two weeks to study the
course of the condition.

TREATMENT
The lack of an effective antiviral treatment for

canine distemper vaccine. In most pups, the concentration of maternal antibodies reaches low
levels at six to eight weeks of age, but they may
be found until 14 weeks of age. As it is usually
not practical to determine the concentration of
maternal antibody, vaccination against CDV
every three to four weeks between six to 16
weeks of age is recommended, followed by
periodic boosters (Greene and Appel 1990).However, vaccination breakthroughs may occur. More
than half of the current dogs with neurological
distemper had been vaccinated against CDV. In
addition, post vaccinal encephalitis has been
reported after distemper vaccination (Hartley
1974).

CDV infection requires the need for supportive

care and symptomatic treatment. The patients

should be kept clean, warm and quiet. Fluid therapy should be given to dogs with altered hydration status. Sometimes a parenteral nutrition
programme is necessary. Dogs with respiratory
signs and with secondary bacterial bronchopneumonia must be given antibiotics. Vitamin B may
counteract anorexia.
In patients with seizures, anticonvulsants such
as phenobarbitone should be administered, but
the response is often poor. Corticosteroids are
used because of the immunopathological basis of
the neural lesions and their potential to combat
brain oedema. The immunosuppressive effect of
steroids can also be a disadvantage, because the
inflammatory response does lead to clearance of
the virus (Bollo and others 1986).
Many drugs have been used for the treatment
of myoclonus, such as procainamide or clonazepam, without much success and it is thought
that myoclonus is probably an irreversible
condition.
Passive administration of canine hyperimmune
serum may be beneficial to combat viraemia and
perhaps viral replication in extraneural tissues.
However, it is very doubtful that significant
amounts of the administered antibodies cross the
blood-brain barrier. Therefore, serotherapy is
probably not useful in CDV infection of the central nervous system. As macrophages and their
products, especially free radicals of oxygen, are
important in the induction of tissue damage in
distemper (Griot and others 1989), antioxidants
such as vitamin E, vitamin C, superoxide dismutase and iron chelators should perhaps be used
therapeutically, but clinical trials with such
drugs have not yet been performed.
It is clear that prevention of the disease is possible through active immunisation. Maternal
antibodies are responsible for a period of temporary immunity that varies in duration from a few
days to four months (Shell 1990). During this
time these anti-CDV antibodies prevent both
infection and successful immunisation with

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469

A. TIPOLD AND OTHERS

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VIDEO REVIEW

gnosis of this condition is only achieved by biopsy (unless one has seen it before). The four difficult cases which are discussed are atopy, drug
eruption, pemphigus foliaceus and vasculitis.
This last case nicely illustrates the point that
although the pathological process may be identified the underlying cause may still be elusive. In
both of these videos the authors talk the viewer
through their thought processes, and with a fair
degree of success. One must accept that videos
can never capture the essence of a diagnosis;
only being in the consulting room can achieve
that.
On the whole the format is successful and the
productions are useful. The photography is good
and the close-ups of the lesions particularly so.
The use of overlays to summarise the case history
or laboratory tests, for example, is very effective.
Some aspects of the production are less pleasing.
In particular the cutting between besuited clinician in the office to clinicians in consulting
tunic. This gives a somewhat disjointed feel to
the flow of the material and this reviewer and
one suspects the clinicians, would have felt more
comfortable with the discussions taking place in
the consulting room.
The tapes are supplied with a small booklet
which contains a few questions and seven summarised case histories. The presumption is that
the viewer will be in a position to answer these if
the information in the video productions has
been understood.
These two video productions will prove useful
to clinicians who require guidance on how to
apply investigative dermatological techniques to
clinical case material and the production is to be
commended.
RICHARD HARVEY

1-8

VANDEVELDE,
M., ZURBRIGGEN,
A., HIGGINS,
R. J. & PALMER,
D.
(1985) Spread and distribution of viral antigen in
nervous canine distemper. Acta Neuropathologica 67,
211-218
VANDEVELDE,
M., ZURBRIGGEN,
A., STECK,
A. & BICHSEL,
P. (1986)
Studies on the intrathecal humoral immune response in
canine distemper encephalitis. Journal of NeuroimmunolOgy11, 41-51
WOLF, M., CACHIN,
M., VANDEVELDE, M., TIPOLD, A. & DUBEY,
J. P. (1991) Zur klinischen diagnostik des protozoaren
myositissyndroms (Neospora caninum) des welpen.
Tierh'rztliche Praxis 19, 302-306

Diagnosis in Small Animal Dermatology: Part 3,

Four Easy Cases (26 minutes) and Part 4, Four
Difficult Cases (32 minutes). Written by D. H.
Scarff and I. S. Mason. Produced and distributed
by the Royal Veterinary College Unit for Veterinary Continuing Education. Price 3 5 . 0 0 each
(plus p&p and VAT).

THESE two videos provide a follow-up to the

guidance offered in the first two of the series
which dealt with the basics of dermatological
diagnosis ie, history, physical examination and
laboratory tests. The presentations talk the viewer through a series of progressively more difficult
diagnoses.
In each video the cases are presented in a similar format with a brief introduction and a summary of the case history. The pertinent details of
the clinical examination are demonstrated and
the viewer is then requested to stop the tape and
suggest a differential diagnosis. This is then discussed and the viewer is then prompted again,
this time to list the investigative tests that will
eliminate the differentials. The information is
then collated and the definitive diagnosis briefly
discussed. Treatment and case management are
not detailed.
The four easy cases presented are scabies, flea
allergic dermatitis, hyperadrenocorticism and
feline plasma cell pododermatitis. The choice of
the latter two as easy cases may cause raised eyebrows on some circles. Feline plasma cell pododermatitis in particular is very rare, but,
notwithstanding, the choice of this condition to
illustrate diagnostic work-up is, perhaps, surprising, as the presenters admit. The definitive dia470