Degenerative and Metabolic Brain Disease Flashcards
In utero viral infection effect on cerebellum
Atrophy
Cerebellar abiotrophy - premature degeneration of cells at 2-6 months
Hypoplasia - associated with FPV
Symmetric non-progressive cerebellar signs developing at 2 weeks of age
–> reduced purkinjie fibre and granular cell development
Reported anomalous or degenerative cerebellar diseases
Neuroaxonal dystrophy - GSD, Rottweilers <1y
Inherited hypoplasia - Irish Setter
Intracranial Arachnoid cyst
COMS - can cause cerebellar compression in severe cases
Degenerative Primary Brain disease
Breeds think Lab, JRT, Fox terrier
Myelinopathy (hypo, dysmyelination or myelinolytic)
LEUKODYSTROPHY - inherited myelin defect (Labradors, Poodles 3-6mo)
DDx shaker pups (generalised tremors that improve with age)
Paraparesis/tetraparesis at 3-6months
SPONGY Degeneration –> splitting of myelin sheaths
Axonopathy
–> affects both motor and sensory fibres
JRT, Scottish Terrier, Labrador
Spongiform polioencephalopathy
–> vacuoles of neuropil in neurons
or vacuoles in myelin
Early onset form in Rottweilers <2 months
Aus Cattle dogs <1y
Difference b/w hydrocephalus and hydrancephaly
Hydro = internal accumulation of CSF in ventricles or enlarged area of subarachnoid space
Due to increased CSF pressure
Hydrancephaly = loss of neuroepithelial cells –> reduced thickness of cerebrum and filling of deficit with CSF
- caused by in utero or perinatal destructive process
Causes of Hydrocephalus
Congenital is most common
–> increased intracranial volume before the calvarium fuses –> persistent fontanelle
May not have neurological deficits on exam but difficulty with learning
In recent Chihua hua study, Number of affected cranial sutures was higher and total fontanelle area larger in dogs with low body weight, larger lateral ventricles , and more severe neural tissue compression at the craniocervical junction
Acquired - can be more difficult to identify and may cause diffuse forebrain signs due to increased ICP
–> result of CSF outflow obstruction that can be due to neoplasia, inflammatory debris, FIP solidification of CSF
Tx for hydrocephalus
Indicated in animals with moderate to severe static signs of neurological deficits or in those with progressive signs
Though seizure prevalence in congenital disease reported to be low.
Anti-inflammatory steroids
Acetazolamide (carbonic anhydrase inhibitor) used short term
VP shunt - % decrease in ventricular size associated with resolution of ataxia and obtundation
–> complications ~15% kinking or obstruction
Presentation of inborn errors of metabolism
Cause an interference in normal cell function –> premature death of neurons
Typically waxing and waning signs, often with seizures and altered mentation (forebrain)
Severity may be affected by diet
Possible tests to look for inborn errors of metabolism
Increased serum ammonia in urea cycle enzyme deficiencies
Ketonuria without hyperglycemia –> may indicate mitochondrial metabolism defect
Urine metabolite concentrations
What is organic aciduria
Inborn errors in metabolic pathways –> increased levels of organic acids in urine
Best example is congenital B12 malabsorption.
Vital cofactor for Methionine synthesis and Proprionyl conversion
Deficit –> increased MMA which is also increased in urine. and increased HCY
Same as for B12 acquired deficiency but symptoms occur in first year of life (from 2-12months)
Hypersegmented neutrophils and anemia also reported due to effects on haematopoietic maturation
Can also see elevated NH3 due to need for B12 in urea cycle
Seen in Beagles, Giant Schnauzers, Border Collies
DNA tests available.
Lysosomal storage disease - aetiology and presentation
Accumulation of metabolic biproducts (sphingolipids, glycolipids) within lysosomes of neurons
–> a result of metabolic enzyme deficiency affecting normal b/d
These accumulate in neural and visceral tissue but because of high metabolic demand and absnece of cell turnover neurons are more susceptible.
Often present with cerebellar symptoms first due to their requirement of rapid input on sensory feedback
Retinal lesions or cataract formation are also reported
Bony or connective tissue abnormalities
Mucopolysaccharidosis can cause atypical appearance of neutrophils
–> JVIM 2020 reported in faily of Golden retrievers
MRI - always symmetrical
Insidious progressive diseases that are always fatal
Many different genetic mutations causing accumulation of different biproducts
Ceroid Lipofuscinosis cause and presentation
A type of lysosomal storage disease –> lysosomal dysfunction prevents protein breakdown–> accumulate hydrophobic proteins
which autofluoresce (similar to ceroid and lipofuscin pigments seen with normal aging but these are not actually present)
Later onset than other LSD at 1-2y
Breeds Dachshund, Border Collie and Aus Shep
Present with progressive visual impairment, decline in cognition and seizures
Generalised brain atrophy on MRI (cerebrum and cerebellum)
Progressive and fatal
Lafora disease - aetiology, presentation and recent publications
Breeds - Mini Wirehaired Dachshund
Autosomal recessive mutation
Also Miniature poodle, Pointer, Bassett Hound
Slowly progressive (avg onset 7-9y) course of disease
- mental decline with loss of house training
- difficulties learning new tasks
- increased photo and noise sensitivity
–> seizures in response to visual or auditory stimuli
(myoclonic seizures with muscular twitching and muscle fasciculations which can progress to full seizure.
- Later onset deficits of impaired vision and hearing and coordination
Caused by mutation in laforin starch binding phosphatases –> accumulation of poorly branched glycogen in neurons with highest density in the thalamus
Causes of and Pathogenesis of neurological signs in Thiamine deficiency
Thiamine (B1) - water soluble vitamin, not stored and can be lost in urine. Cats have a 3x higher requirement compared to dogs
High levels in meat/plants protein so readily acquired from diet
UNLESS: thiaminases found in raw fish or sulphate preservatives used that destroy thiamine
Or fed vege diet
Thiamines biological roles are in glycolysis (production of pyruvate and converting pyruvate to Acetyl CoA) and in the citric acid cycle
Medications can also impact thiamine absorption: pyrimethine for protozoal infections
Deficiency results in metabolic derangements
–> lactic acidosis due to reduced ability to convert pyruvate to acetyl CoA –> less for TCA thus make lactate
–> inefficiency of the TCA –> impacts neurons first because of their high energy requirement.
Symptoms/Diagnosis of Thiamine deficiency
can start to see symptoms within 1 week of dietary change
–> non-specific GI upset
–> progressive neurological signs of ventroflexion, mydriasis, seizures, vestibular signs, acute blindness, hyperaesthesia
May also see alterations in heart rate.
Bloods: hyperlactataemia due to reduction in TCA precursors
Low serum thiamine (may not reflect tissue levels which can be measured separately)
–> serum represents only 10% of the whole body thiamine and it is mostly inactive so this is not the test of choice
Increased transketolase activity in erythrocytes (as increased concentration of precursors for the pentose phosphate pathway)
can measure thiamine content in diet to prove theory
Imaging: symmetrical haemorrhage and necrosis of grey matter brainstem nuclei –> hyperintense T1W due to haemorrhage
Treatment trial is often the most practical test - results in rapid improvement
AVJ study on breeds most often affected by ABCB1 MDR mutation found
Collies, Aust Shep, White Swisse Shep and Shetland sheepdogs to be most commonly affected breeds in their population
Non herding breeds - 1 labrador and 1 Cocker spaniel both heterozygotes
