Page 807 - Clinical Small Animal Internal Medicine

71 Disorders of the Forebrain 775

Degenerative and
VetBooks.ir Developmental Causes

Storage Diseases
There are a large number of diseases caused by congenital
deficiencies in the enzymatic pathways that are involved
in degrading lysosomal waste products within cells. The
biochemical pathways involved are complex but the
majority of described storage diseases involve a defi-
ciency of a lysosomal acid hydrolase enzyme. A deficiency
in any one enzyme leads to a build‐up of undegraded
products within lysosomes in the cell’s cytoplasm which
ultimately enlarge and cause the death of the cell.
Although cells in all body organs are affected, neurons are
especially vulnerable since they are postmitotic, perma-
nent cells. Most of these conditions affect young animals
at early ages, affect both males and females, and are
autosomal recessively inherited. Most commonly, the ini- Figure 71.1 Histopathology of the cerebellum of a dog with L2‐
hydroxyglutaric aciduria. Note the vacuoles in the Purkinje cell layer
tial clinical signs are referable to cerebellar dysfunction and molecular layer as well as the deep cerebellar white matter.
but two in particular, alpha‐fucosidosis and ceroid lipo-
fuscinosis, may show up with signs of forebrain disease with both males and females affected and with some
initially, including behavioral changes, dullness and vision dogs presenting in middle age.
abnormalities (typically abnormal depth of vision or ina- The condition is caused by an inborn error of metabo-
bility to focus rather than blindness), followed by general- lism leading to widespread vacuolation within neurons
ized ataxia, dementia, tetraparesis, tremors, and seizures. in the brain with excess secretion of L2‐hydroxyglutaric
Affected breeds include border collies, Tibetan terriers, acid in the urine (organic acid). Diagnosis may be
English setters (ceroid lipofuscinosis), and springer span- suggested by magnetic resonance imaging (MRI) finding
iels (alpha‐fucosidosis). (lack of distinction between gray and white matter on
In alpha‐fucosidosis, the diagnosis can occasionally be T2‐weighted MRI scans with diffuse cerebral atrophy)
made on hematologic examination (40% of lymphocytes and demonstration of excess organic acid in the urine,
may have cytoplasmic vacuoles) or genetic testing. In and genetic testing is now available (Figure 71.1). Overall,
ceroid lipofuscinosis, skin biopsy and demonstration of the long‐term prognosis is guarded as the condition is
autofluorescent pigment may confirm the diagnosis. untreatable but some dogs with mild signs may live a
Imaging studies and cerebrospinal fluid (CSF) taps are relatively normal life if seizures are controlled with anti-
typically normal and CSF may be normal or show vacu- convulsant medication.
olated macrophages (alpha‐fucosidosis). Generally, these
diseases are progressive and nontreatable, with death
occurring by the second or third year of life, although Anomalous Causes
gene therapy has been shown to reverse clinical signs in
a feline model of alpha‐mannosidosis, suggesting gene
therapy may one day become available. Hydrocephalus
Hydrocephalus is a pathologic enlargement of the ven-
L2‐Hydroxyglutaric Aciduria tricles as distinct from ventriculomegaly which describes
enlargement of the ventricles which may or may not be
This is a poorly characterized condition reported over pathologic (there is considerable breed‐related variation
the past 10 years in young to middle‐aged Staffordshire in ventricular size, with brachycephalic dogs such as
terriers. Initially reported in the UK, the disease has now boxers and bulldogs often having larger ventricles than
been seen worldwide. Clinical indications include vague other breeds). True hydrocephalus may occur due to
prosencephalic signs – abnormal behavior, anxiety, dif- obstruction in the ventricular system (obstructive or
ficulty/slowness in learning (owners may describe these noncommunicating form; most common) or overproduc-
dogs as dull), and an abnormal, ataxic gait (difficult to tion of CSF from tumors of the arachnoid granulations
localize). Signs may also include seizures in some cases. and choroid plexus (nonobstructive or communicating
The onset of the condition is from 6 months onwards, hydrocephalus; less common).