Intention tremors due to cerebellar disorders

By | January 31, 2015

Tremors that occur when an animal intends to move in a goal-orientated activity are most often the result of cerebellar disease ().

Degenerative diseases

Cerebellar cortical degeneration

Cerebellar cortical degeneration, also termed cerebellar abiotrophy, is usually an inherited disease in dogs () with few reports in cats. Primary cerebellar cortical degeneration refers to degeneration and loss of Purkinje cells, molecular cells and granule cells.

Clinical signs: These diseases are recognized syndromes in American Staffordshire Terriers, American Pit Bull Terriers, Kerry Blue Terriers, Gordon Setters, Rough-coated Collies, Border Collies, Brittany Spaniels, Bullmastiffs, Old English Sheepdogs and occur rarely in Samoyeds, Airedales, Finnish Harriers, Labrador Retrievers, Golden Retrievers, Beagles, Cocker Spaniels, Cairn Terriers, Great Danes, Scottish Terriers and others ().

Clinical signs usually begin between 3 and 12 months of age. However, a subset of adult onset diseases occur with signs starting from 2-8 years of age in the Brittany Spaniel (), Gordon Setter (), Old English Sheepdog (), American Staffordshire Terrier () and Scottish Terrier (). Other signs of cerebellar disease that accompany cerebellar tremor include ataxia, dysmetria, menace deficits, head tilt, nystagmus (), truncal sway and infrequently anisocoria. Clinical signs associated with degenerative cerebellar diseases progressively worsen.

Pathogenesis: Abiotrophy is a process by which cells develop normally but later degenerate because of an intrinsic cellular defect necessary for continued life of the neuron (). Many of these diseases may result from underlying abnormalities of cellular metabolism or cellular function (such as calcium and potassium channelopathies) and they are known to be inherited in American Staffordshire Terriers, Old English Sheepdogs, Gordon Setters and Brittany Spaniels.

Diagnosis: Ante-mortem testing for these diseases often results in negative or normal findings. Definitive diagnosis is usually rendered only at necropsy and histopathological examination of the nervous tissue. In some instances of cerebellar atrophy a smaller than normal cerebellum may be seen on MR imaging of the intracranial nervous system (). This is most readily seen on the sagittal view. CSF with these degenerative cerebellar conditions is normal.

Treatment and prognosis: There are no effective treatments for this group of disorders and the prognosis is guarded to grave.

Storage diseases

Storage diseases can result in cerebellar degeneration ().Cellular products accumulate and affect neuronal cells physiologically or mechanically resulting in cellular dysfunction, and hence, clinical signs. Clinical signs are of a progressive cerebellar disease. Diagnosis is based upon biopsy or necropsy. No treatment is effective. Breed specificities are documented in site.

Neuroaxonal dystrophy

Clinical signs: This is a disease of Rottweiler dogs () but is also reported in Collies, Chihuahuas, Boxers, German Shepherd Dogs, Siamese and a family of domestic cats. In Rottweilers neuroaxonal dystrophy is characterized by cerebellar signs (ataxia, hypermetria, loss of menace, head tremor) beginning at 1-2 years (ataxia) and progressing over the next 2-4 years (menace deficits, intention tremor). Conscious proprioception remains intact.

Pathogenesis: The underlying pathogenesis is unknown. The cell bodies in the grey matter are affected (axonal spheroids) throughout the nervous system except the cerebral cortex. The most severe lesions are in the spinocerebellartracts and the Purkinje cells.

Diagnosis: The diagnosis is usually established at post-mortem; however, ante-mortem biopsy of these areas may show pathological changes. Recognition of the characteristic clinical signs in young Rottweilers is suggestive of this disease, but a full diagnostic work-up (imaging and CSF analysis) is needed to rule out diseases that may be treatable (e.g. encephalitis). It is important to note that Rottweilers also suffer from a neurodegenerative disease called leucoence-phalopathy, which causes progressive tetraparesis in young (1-4-year-old) Rottweilers (). Younger Rottweilers (3-8 months) can develop a disease called neuronal vacuolation, which causes a combination of laryngeal paralysis, progressive tetraparesis and microphthalmia ().

Treatment and prognosis: No treatment is known and the long-term prognosis is poor.

Anomalous diseases

Congenital malformations of the cerebellum are occasionally seen. These include aplasia (an absence of cerebellar tissue) and partial agenesis or hypoplasia (partial or uniform lack of cerebellar tissue). Cerebellar hypoplasia has been associated with infection or toxin exposure during a critical stage of cerebellum development in-utero. Caudal vermian hypoplasia is described in some dogs with associated ventricular dilation (Dandy Walker-like malformation) (). Cerebellar hypoplasia has been recognized in Chow Chows, Irish Setters and Wire-haired Fox Terriers. The latter two breeds may have concurrent lissencephaly. Cerebellar aplasia has been reported in Siberian Huskies. Herniation of the cerebellar tonsils is a component of Chiari-like malformations that have been reported in various small breed dogs but in particular in Cavalier King Charles Spaniels ().

Feline cerebellar hypoplasia

Clinical signs: Clinical signs are most apparent when the animal begins purposeful movement and attempts to walk. Tremor accompanying the disease usually has a slower frequency (2-6 times per second) and larger amplitude. The tremor worsens (increases in frequency or amplitude) when the cat moves in a goal-oriented way (e.g. bends down to eat). Other signs include ataxia, hypermetria, menace deficits, head tilt and nystagmus. Clinical signs usually remain static or improve with growth as the cat compensates, causing the tremor to become less apparent.

Pathogenesis: Feline cerebellar hypoplasia is caused by in-utero infection with the panleucopenia virus (parvovirus), which affects the external germinal layer of the cerebellum and prevents the formation of the granular layer (). Some affected cats have concurrent hydrocephalus and hydranencephaly. Infection of the fetus may occur when a pregnant queen is inoculated with a modified-live panleucopenia virus vaccination, which also destroys the external germinal layer of the cerebellum and prevents the formation of the granular layer.

Diagnosis: Ante-mortem testing for this disease often results in negative or normal findings. Occasionally, inflammatory cells may be present upon CSF examination in cats with active panleucopenia viral infection. CSF with the other degenerative cerebellar conditions and with non-active panleucopenia infection is usually normal. MRI evaluation can confirm the presence of a small cerebellum but it is not specific for this disease.

Treatment and prognosis: There is no treatment for this disorder. Some cases are mild but others can be quite severe, and in these cases walking and eating may be very difficult. As the signs do not progress with time the prognosis may be fair if the animal is only mildly affected. As prevention, it is important not to inoculate queens with a modified-live panleucopenia virus vaccine.

Neonatal ataxia in Coton de Tulear dogs

Clinical signs: Clinical signs become evident at 2 weeks of age once the puppies start to move around (). They include head and intention tremors, severe ataxia and vertical nystagmus. The signs are not progressive but are so severe that most dogs cannot walk and are euthanized.

Pathogenesis: This is currently unknown but the disease is suspected to be an autosomal recessive disease that causes abnormal cerebellar development.

Diagnosis: The diagnosis is by recognition of the clinical signs and ruling out other possible causes. Histopathological findings may be minimal using light microscopy but electron microscopy reveals synaptic abnormalities.

Treatment and prognosis: There is no effective treatment at this time. Although the disease is not progressive the signs are so severe that the prognosis is grave.

Neoplastic diseases

Primary or secondary neoplasia involving the cerebellum is uncommon. More common is primary neoplasia of the inf ratentorial region that may affect the cerebellum and includes meningioma and choroid plexus tumours. These tumours arise from the meninges and the choroid plexus of the fourth ventricle, respectively. Gliomas and medulloblastomas rarely involve the cerebellum in dogs. Other mass lesions such as dermoid and epidermoid cysts may arise within or around the fourth ventricle and compress the cerebellum. Diagnosis is afforded with advanced imaging studies such as MR or CT (). See site for a full discussion of the treatment of brain tumours.

Inflammatory diseases

The cerebellum can be involved with the same infectious and immune-mediated processes that result in encephalitis (). See site for a full description of these diseases. The cerebellum may also be affected by inflammation with the generalized tremor syndrome in dogs, described previously, and indeed this syndrome has been called idiopathic cerebellitis by some authors. No definitive cause for this inflammation has been elucidated.

Presumed immune-mediated cerebellar granuloprival degeneration in Coton de Tulear dogs

Clinical signs: In this unusual disease of male Coton de Tulear dogs, onset of progressive cerebellar signs was noted at 8 weeks of age ().

Pathogenesis: Clusters of T lymphocytes were identified in the cerebellar cortex leading to the proposal that this disease results from a genetically determined immune reaction against the granule cells.

Diagnosis: The diagnosis is obtained by histopathological evaluation of the brain post-mortem.

Treatment and prognosis: No treatment has been reported. Prognosis is grave.

Toxic diseases

With the exception of metronidazole, toxicity rarely specifically affects the cerebellum but cerebellar dysfunction may be part of the clinical syndrome of many toxin exposures. (See section above on the aetiology of tremors.)

Metronidazole toxicity

Toxicity with metronidazole may result in central vestibular and cerebellar signs in both dogs and cats (). This can be associated with doses as low as 30 mg/kg/day. As metronidazole is metabolized by the liver, toxic serum levels can occur with lower doses in animals with liver dysfunction. Ataxia is usually the initial clinical sign, progressing to nystagmus and more severe vestibular and cerebellar dysfunction. Clinical signs often reflect central vestibular dysfunction and morphological lesions have been found in the brainstem of affected animals ().

Vascular diseases

Thromboembolic and vascular disease can involve the cerebellum (). Clinical signs often occur acutely, and rarely cause tremors alone ().

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