WHS: Wobbly Hedgehog Syndrome

WOBBLY HEDGEHOG SYNDROME IN AFRICAN PYGMY HEDGEHOGS (Atelerix spp.)

Donnasue Graesser Ph.D
Terry R. Spraker DVM, Ph.D., Dipl. ACVPb,
Priscilla BDressen DVMc,
Michael M. Garner DVM, Dipl. ACVPd,
James T. Raymond DVM, MS, Dipl. ACVPa, b, c, d,
Gordon Terwilliger BSa, b, c, d,
Jung Kim MDa, b, c, d and
Joseph A. Madri MD, Ph.D.a, b, c, d

A. Yale University School of Medicine, Departments of Pathology and Comparative
Medicine, New Haven, CT 06510 USA

B. Colorado State University Veterinary Diagnostic Laboratory,
Fort Collins, CO 80523 USA

C. NorthStar Veterinary Clinic
Fort Collins, CO 80525 USA

D. Northwest ZooPath
Monroe, WA 98272 USA.

Available online 18 March 2006.

ABSTRACT:
Wobbly Hedgehog Syndrome (WHS) is a progressive paralysis that occurs in
approximately 10% of pet African hedgehogs in North America. Clinical signs
of WHS begin with mild ataxia, progress to more severe neurologic signs, and
ultimately lead to complete paralysis. The onset of WHS commonly occurs under 2
years of age, but can occur at any age. Progression rate is variable, and the
majority of hedgehogs are completely paralyzed by 15 months after the onset of
clinical signs. WHS can only be definitively diagnosed by post-mortem
examination of tissues from the central nervous system. The characteristic
histopathology of WHS is vacuolization of the white matter of the brain and spinal
cord, and associated neurogenic muscle atrophy. There is no inflammation of
the central nervous system associated with WHS. The etiology of WHS is
unknown, but pedigree analysis indicates a familial tendency to the disease.

KEYWORDS: Atelerix; hedgehogs; wobbly hedgehog syndrome;
paralysis; paresis; demyelination.

Article Outline
Clinical Signs and Statistics
Pathology
Gross Observations
Histopathology
Treatment
Discussion
Acknowledgements
References

African pygmy hedgehogs are becoming increasingly popular pets in North America,
as well as in South America, Europe, and some Asian countries. Pet
African pygmy hedgehogs in North America belong to the genus Atelerix, and
include central African hedgehogs (Atelerix albiventris), Algerian hedgehogs
(Atelerix algirus), and hybrids of the two species. African hedgehogs have also
been utilized as a research species in the United States, because they possess a
protein similar to human lipoprotein(a).1

Since the mid-1990s, a condition characterized as progressive paralysis or
degenerative myelopathy has been observed in pet African hedgehogs.2, 3, 4
and 5 This condition has been coined Wobbly Hedgehog Syndrome (WHS).3, 4 and 5 A
similar disease has been reported in European hedgehogs (Erinaceus europaeus).5
and 6 We have evaluated the clinical histories and post-mortem
histopathology of a large sampling of African hedgehogs with WHS, and a report,
we provide an overview of the clinical signs and progression of WHS, and
a brief description of the pathology underlying the disease.

CLINICAL SIGNS AND :
In a survey of owners of pet African hedgehogs between the years 2000 and 2005,
10% of hedgehogs (n = 676) were reported to have some degree of progressive
paralysis. Detailed clinical histories were obtained for 61 of
the animals that demonstrated neurologic signs, and 45 cases were
submitted for post-mortem examination. In 5 of these cases, the neurologic signs
resulted from unrelated pathology, generally brain tumors. The remaining 40 cases demonstrated similar
lesions of the central nervous system (CNS), which are discussed in the Pathology
section below. Clinical statistics were derived only from the 40
hedgehogs confirmed to have these characteristic lesions. The study consisted
of 22 females and 18 males. There is no statistical evidence for
gender bias of WHS.

One of the earliest indicators of WHS in hedgehogs is the inability to close the
hood. On examination, hedgehogs with WHS first present with mild ataxia,
frequently described as lack of coordination, becoming off balance,
stumbling, tripping, or wobbling. In early stages of WHS, the clinical signs are
usually relapsing and remitting. Over several months, the signs become
progressively more severe and may include falling consistently to one side,
tremors, exophthalmos (Fig 1), scoliosis, seizures, muscle atrophy, self-
mutilation, and difficulty regulating body temperature. In 70% of the cases in
this study, the paralysis was ascending from hindlimbs to forelimbs. Two hedgehogs
had no clinical signs, but were included in this study based on the
appearance of characteristic histopathologic lesions. A synopsis of the
primary clinical signs of WHS is presented in Table 1. To better appreciate
the appearance and movement of a hedgehog with WHS, a video clip can be
viewed at the following web site: http://www.wobblyhedgehog.org.

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Figure 1. Unilateral exophthalmos, protrusion of one eye, is a common feature
of hedgehogs with WHS, occurring in 28% of the cases in this
study.
Photo courtesy of Teresa Johnson.

Table 1.

Occurrence of Clinical Signs in Hedgehogs with Wobbly Hedgehog Syndrome:
Clinical sign Frequency (n = 40) Percentage
Lack of coordination 38 95%
Significant weight loss 35 88%
Dysphagia in late disease 31 78%
Falling to one side 28 70%
Paralysis was ascending 28 70%
Tremors 26 65%
Unilateral exophthalmos 11 28%
Curvature of spinal column 9 22%
Seizures 8 20%
Self-mutilation or aggression 4 10%
No neurologic signs 2 5%

All cases included in this table were determined to have characteristic WHS
histologic lesions in the CNS by post-mortem examination.

The progression of WHS is generally accompanied by severe weight loss. However,
in most cases, there is no apparent loss of appetite until the
terminal stages of the disease, when most hedgehogs become dysphagic (Table 1).
Unless there is other complicating pathology leading to the death of the
hedgehog, the end result of WHS is tetraplegia with muscle atrophy (Fig 2).
Many owners choose euthanasia when the hedgehog becomes significantly immobile
and quality of life is compromised. However, some owners choose supportive care
and hand-feeding (Fig 3). A hedgehog that has progressed to tetraplegia, but is
not yet dysphagic, can live for several months with supportive care.

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Figure 2. Hedgehogs in final stages of WHS. (A and B) Each of these hedgehogs has
suffered from the progressive paralysis associated with WHS over several months,
and demonstrates many clinical signs typical of the final stages of the
disease including tetraplegia, muscle atrophy, and obvious emaciation.
Photos courtesy of Donna Pate and Laura Ledet.

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Figure 3. Supportive care of hedgehog with WHS.
This hedgehog is immobilized because of WHS, yet she is able to eat and drink with
assistance. With hand-feeding and supportive care, hedgehogs with WHS can
survive for many months.
Photo courtesy of Sarah Shore.

WHS occurs most frequently in hedgehogs under 2 years of age, but can present at
any age (Fig 4). The average age for onset of clinical signs of WHS in this
study was 18.5 months (range, 1-36 months). In 60% of cases, the hedgehog was
immobile within 9 months after the onset of ataxia (Fig 5). In 90% of cases,
immobility occurred by 15 months after the onset of ataxia. There was no
correlation between age at onset and progression rate. We also surveyed owners
of hedgehogs with WHS for information on dietary regimens,
treatments, and supportive therapies, and have not demonstrated any correlation
between these variables and progression rate.

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Figure 4. Age at onset of clinical signs of WHS.
Thirty-four of the hedgehogs in this study had a known birth date. Most commonly,
clinical signs of WHS first appeared before 2 years of age. WHS may occur in
older hedgehogs as well.

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Figure 5. Progression to immobility in WHS.
Thirty-seven of the hedgehogs in this study progressed to significant paralysis.
(Two hedgehogs had typical WHS lesions, but no clinical signs. In 1 case, death due
to lymphosarcoma preceded full progression of WHS). This graph indicates
the time of progression from onset of clinical signs to immobility of
the hedgehog.

PATHOLOGY:
Although the clinical signs described above are typical of hedgehogs with WHS,
currently, definitive diagnosis of WHS can only be made by post-mortem
histopathologic examination of the CNS. Other reported causes of progressive
paralysis in hedgehogs have included various brain tumors, intervertebral disc
disease, and hepatic encephalopathy.

Following is a description of the characteristic pathology of WHS.

GROSS OBSERVATIONS:
The average range of animals submitted for postmortem examination was between 200 and
300 g. Hedgehogs were usually emaciated with varying degrees of skeletal muscle
atrophy of the limbs and spinal column. Occasionally, abrasions to the toes of the
paws could be seen. These abrasions were most likely the result of the animal
dragging its limbs because of loss of full range of motion and inability
to fully extend the limbs.

Slightly enlarged and pale livers were common. Many animals had a roughened,
pitted surface to the cortex of the kidneys. Pale triangular lesions could
often be visualized within the renal cortex. Gross lesions were not observed in
the brain, spinal cord, heart, lungs,
digestive system, endocrine system or reproductive system except when
nonrelated tumors were present.

HISTOPATHOLOGY:
Forty-five hedgehogs presumed to have WHS were submitted for post-mortem
histopathologic examination. No evidence of WHS was found in 5 of these
hedgehogs: 1 hedgehog was diagnosed with fibroblastic meningioma; 3 with
astrocytomas; and 1 with severe hepatic lipidosis and hepatic encephalopathy.

The remaining 40 animals were observed to have similar histologic lesions in the CNS.
The majority of these hedgehogs were in the terminal phase of WHS, although
some were euthanized in earlier stages of the disease. Six (15%) of
these hedgehogs had unrelated tumors in addition to WHS. Two (5%) of the
hedgehogs had no clinical signs and were submitted to the study based on a
family history of progressive neurologic signs. Their cause of death was
unrelated to WHS, yet they possessed CNS lesions compatible with early
WHS. The following is an overview of the histologic lesions
characteristic of WHS.

The primary histologic lesion in hedgehogs with WHS is vacuolization of the white
matter tracts of the cerebrum, cerebellum, and brain stem (Fig 6). The
lesion also occurs in the white matter tracts throughout the spinal cord (Fig 7).
There appears to be a loss of myelin first, then secondary degeneration
and loss of the axon, followed by neuronal degeneration. The
affected regions are quite extensive, especially in the corona radiata of the
cerebrum and the white matter of the cerebellum, brain stem, and spinal cord.
There is also a degeneration and loss of lower motor neurons of the ventral
horns of the spinal cord. Demyelination is also found in the ventral rootlets,
but is not a feature in the dorsal rootlets and spinal ganglia or peripheral ganglia.
There is little to no evidence of peripheral neuropathy. Inflammation is
not a feature in the brain or spinal cord in hedgehogs with WHS, except mild
astrocytosis in the brain.

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Figure 6. Cerebrum of a hedgehog with WHS.
Hematoxylin and eosin stain of a thin section of cerebrum from a hedgehog with
WHS. Note the extensive spongiosis of the white matter tracts of the corona
radiata. (20 × magnification)

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Figure 7. Spinal cord of a hedgehog with WHS.
Hematoxylin and eosin stain of a thin section of spinal cord from a hedgehog with
WHS. Note the extensive areas of demyelination in the lower medial tracts
and the lateral central tracts. (4 × magnification)

The primary lesion found in skeletal muscle is neurogenic atrophy of myocytes, without
inflammation. These myocytes are eosinophilic and triangular.

Hepatic and renal pathology is also seen in some of the hedgehogs with WHS. Mild to
severe hepatic lipidosis is present in 20% of the cases. There is no inflammation
associated with these areas of centrilobular fatty degeneration. Also
common are multiple areas of renal cortical infarction. These are wedge-shaped
regions in the cortex that are characterized by tubular degeneration and
moderate infiltration of lymphocytes and plasma cells within the
interstitial tissues. Glomerulosclerosis is often present within
the areas of infarction. These hepatic and renal lesions are not found in all hedgehogs with WHS. They may be an
incidental finding, because similar lesions are occasionally present in
hedgehogs without WHS pathology.

TREATMENT:
Numerous treatments for WHS have been attempted with little or no success. The
most commonly reported therapies were supplementation with vitamin E,
selenium, vitamin B, and/or calcionate syrup. Oral predisone was often prescribed.
Antibiotics, including trimethoprim sulfa, Amoxi-Drop Liquid
(Pfizer Animal Health, New York), and Baytril (Bayer, Animal Health Division,
Shawnee, KS), were sometimes prescribed to treat concurrent infections. In addition,
many hedgehogs have been treated with homeopathic remedies,
acupuncture, and physical therapy regimens. Some of these treatments appeared
to ameliorate the clinical signs temporarily or slow the progression of
paralysis. However, because WHS is a relapsing and remitting disease during
early stages and progression of the disease is variable, evaluation of the
success of treatments is not possible without controlled studies. No treatment
has been shown to stop the progression of paralysis.

Avonex (interferon beta-1a, Biogen Idec, Cambridge, MA) therapy was attempted in 1
case. Beginning 2 weeks after onset of ataxia, Avonex was dosed at weekly
intervals (300,000 u/dose) concurrently with depomedrol (20 mg/mL, 0.02 mL) and
dexamethasone (2.0 mg/mL, 0.03 mL) for a total of 12 treatments. Despite this
treatment, progressive signs appeared within 2 weeks, and the hedgehog was
severely debilitated by 12 weeks.

DISCUSSION:
WHS is a common cause of progressive paralysis in the pet African pygmy hedgehog
population in North America. Other less common causes of progressive
paralysis in hedgehogs include brain
other encephalopathies. WHS can only be definitively diagnosed by post-mortem
histologic examination of CNS tissues. The primary histopathology associated with
WHS is vacuole formation in white matter areas of the brain and spinal cord,
with associated neurogenic atrophy of muscle.

The next most common pathology finding in hedgehogs with WHS is hepatic lipidosis.
There appear to be some nutritional complications to the disease,
given that the hedgehogs are generally emaciated. Hepatic lipidosis in WHS
hedgehogs may be similar to that of emaciated cats and other animals in a
starvation state.7 However, it is also a common finding in African hedgehogs
without WHS,8 so hepatic lipidosis in WHS cases may also be the result of a
species-specific predisposition.

The etiology of WHS is unknown. Potential etiologies for diseases affecting the white
matter of the CNS fall into 2 general categories: acquired disorders and
demyelinating (or dysmyelinating) diseases of genetic/hereditary background.9
Histopathology and study of disease patterns in the hedgehog
population provide some insight into possible causes of WHS.

Acquired disorders of the CNS white matter include infectious diseases such as canine
distemper virus10 and progressive multifocal leukoencephalopathy, a human
disease that is caused by infection of oligodendrocytes by JC virus.11 Autoimmune
diseases such as multiple sclerosis in humans12 and 13 are also
categorized as acquired disorders. WHS is often incorrectly compared with multiple
sclerosis; however, autoimmune inflammation is not observed in the CNS
tissues of hedgehogs with WHS. Electrolyte imbalances may lead to
demyelination, as in a condition known as central pontine myelinolysis in
humans.14 Central pontine myelinolysis is caused by prolonged hyponatremia
followed by rapid sodium correction, and has also been reported to occur in
dogs.15 and 16 Primary demyelination may also occur in response to dietary
deficiency, exposure to toxins, or brain ischemia.

Other demyelinating diseases of the CNS are due to inherited factors such as enzyme
defects in numerous metabolic pathways (for example, Canavan’s disease).17 Mutations in
the gene encoding the proteolipid protein component of myelin cause
dysmyelinating diseases such as Pelizaeus-Merzbacher disease in humans,18
shaking pup in dogs,19 and 20 and similar dysmyelinating diseases in
other animal models.21

Some insight into the possible etiology of WHS is gained from studies of disease
cluster patterns. There are no reports of transmission of WHS between unrelated
hedgehogs sharing living quarters, or in the same household. Even in relatively
large breeding facilities, reported WHS cases are restricted to
defined family lineages (Fig 8). The hedgehogs in this example pedigree were all
separated from their mothers and
littermates at weaning, were distributed geographically throughout the
United States, were up to 34 months of age when they first showed obvious signs
of the disease, and are all deceased. The lack of transmission of WHS between
unrelated hedgehogs, and the tendency of WHS to occur in family lines, strongly
suggests an inherited component to the disease.

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Figure 8. Pedigree of a family lineage with WHS.
This pedigree demonstrates the familial tendency of WHS. The hedgehogs in this
pedigree were reported to the study from diverse geographic locations throughout the
United States. WHS was not reported to occur in unrelated hedgehogs living in the
same household, or sharing cages with these hedgehogs. Females in the pedigree
are represented by circle symbols; males are represented by square symbols.
The presence or absence of WHS signs and lesions is indicated as follows:

filled red symbols = progressive paralysis,
WHS lesions present in CNS;
partially-filled red symbols = progressive paralysis,
histopathology not available;
filled black symobls = no clinical signs,
WHS lesions absent in CNS; open square = no clinical signs,
histopathology not available; question mark = no information available.

Although no evidence of an infectious agent has been observed, the familial tendency of
WHS does not rule out a transmissible component to the disease. It
is possible that the familial pattern is a result of an inherited
susceptibility to an infectious agent, possibly via genes encoding viral
receptors. It is also possible that vertical transmission of an infectious
agent mimics an inherited trait. If so, the incubation period for the agent is
lengthy, because symptoms of the disease may take up to 3 years post-weaning to
appear. In any case, breeding of hedgehogs with presumed WHS, or those
closely related to hedgehogs diagnosed with WHS, is not recommended.

Further studies will aim to more fully describe the pathology of WHS, to elucidate
the etiology of WHS, to analyze the hereditary pattern of disease,
and to investigate treatment options.

ACKNOWLEDGEMENTS:
The authors would like to thank the International Hedgehog Registry
(http://hedgehogregistry.org) for providing pedigree information. This project was
funded in part by the Hedgehog Welfare Society (http://www.hedgehogwelfare.org)
and the Flash and Thelma Memorial Hedgehog Rescue. This project was also
supported by U.S. Public Health Service grant R37-HL-28373.

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204–205. Abstract | Full Text + Links | PDF (61 K)

ADDRESS COPRRESPONDANCE TO:
Donnasue Graesser
Hedgehog Welfare Society
PO Box 242
Chaplin CT 06235.


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