Metabolic encephalopathies: Diagnoses from blood work alone (Proceedings)


Neurons produce their effect by generating and propagating action potentials. In order to do this, they need to have adequate energy supplies (to maintain resting potential and axonal transport) and appropriate concentrations of electrolytes.

Neurons produce their effect by generating and propagating action potentials. In order to do this, they need to have adequate energy supplies (to maintain resting potential and axonal transport) and appropriate concentrations of electrolytes. The brain claims a massive 15% of the cardiac output to supply of oxygen and glucose, and autoregulation carefully controls the actual perfusion of the brain. While it is very unusual to hear a neurologist talk about a diagnostic workup without mentioning MRI and CSF analysis, there are several disorders that will result in abnormalities of either perfusion, glucose or electrolytes, producing severe dysfunction of the brain. These disorders usually cause changes in routine blood work. This presentation will describe these disorders and their classic blood work abnormalities.


Hypoglycemia causes signs of forebrain disease, the severity of which depend both on the rapidity with which the condition has developed and the actual glucose concentration. Typically, hypoglycemic animals behave as we do – sudden drops in glucose cause sympathetic discharge (to trigger gluconeogenesis). As a result, the animal becomes anxious and ravenously hungry, whereas chronically low glucose concentrations cause lethargy. They will also sometimes appear confused and weak. When a critical glucose concentration is reached, the animal will typically develop generalized seizures and lapse into a coma. It is difficult to give a precise concentration at which this happens, because animals can adapt to slow changes in glucose concentrations remarkably well. There are numerous causes of hypoglycemia, but the most common causes without other complicating factors are due to an insulin overdose, either because of an insulinoma (dogs) or a true iatrogenic insulin overdose (most commonly in cats).

Portosystemic shunts and hepatic failure

Liver failure can cause hepatic encephalopathy. Classic signs are again those of forebrain dysfunction – behavioural changes, central visual losses, seizures and ultimately coma. As a general rule, the hallmark of a metabolic disease is that the signs are non-lateralizing and limited to the forebrain, but we have seen many examples of lateralizing and more global neurological signs with hepatic encephalopathy. Classic changes on chemistry panels include the tetrad of hypocholesterolmeia, hypoalbuminemia, low BUN, and low glucose with microcytosis on the blood cell count. It is also common to detect urate crystals in the urine. Animals in fulminant liver failure will have elevations in liver enzymes and will typically be extremely sick (anorexic, polyuric and polydypsic, vomiting). In these cases, neurological signs often take second place to the systemic manifestations of the disease. In contrast, animals with portosytemic shunts, while clearly not thriving, often do not have the same systemic signs and are more likely to present with bneurological signs as the primary problem. The diagnosis is confirmed with a bile acid tolerance test, ammonia levels and ultrasound of the liver. Rectal scintigraphy can be used to calculate the shunt fraction.


Hypocalcemia lowers the threshold for generation of an action potential and so can cause tetany and seizures. Cases with hypocalcaemia tend to have a combination of tremors and seizures and they are often hyperaesthetic. The most appropriate test to perform is to measure ionized calcium but as these cases often present as emergencies, slow IV infusion of 0.5-1.5ml/kg of 10% calcium gluconate (with an ECG to monitor heart hythm) can be administered to see if this helps to control signs. The most common causes of significant hypocalcemia without other obvious metabolic problems are eclampsia, iatrogenic damage to the parathyroids or hypoparathyroidism and nutritional.

Hyper and hyponatremia

Body water content is closely linked to sodium concentrations and profound changes in sodium change intracellular volume and can produce dramatic neurological signs. Cases may present with profound behavioural changes and seizures. In my experience, partial seizures are common. As with all metabolic changes, it is the speed with which the sodium concentrations change that are critical and not uncommonly, over-rapid correction of hypo- or hypernatremia is the ultimate cause of severe neurological deterioration and often death (e.g. myelinolysis following over-rapid correction of hyponatremia). Causes of hyponatremia include whipworm (Trichuris vulpis), Addisons disease and of hypernatremia include adipsia due to hypothalamic disease, hyperaldosteronism, diabetes insipidus and has been reported in association with hypothyroidism.


The relationship between hypothyroidism and neurological signs has been long and contentious. There are reports of hypothyroidism as a cause of seizures and vestibular signs in addition to numerous neuromuscular effects. While the exact pathogenesis is unclear, there are old and recent reports of central vestibular signs associated with hypothyroidism and with the advent of MRI a clear link to vascular disease has been shown in vivo in addition to the historical reports of atherosclerosis detected histopathologically. Severe hypothyroid crises can cause myxoedma coma, with Doberman Pinschers reported to be overrepresented. Changes on blood work include mild anaemia, hypercholesterolemia and mild elevations in ALT. The diagnosis is established by measurement of fT4 and TSH levels. It is not uncommon for dogs with acute onset of neurological signs due to hypothyroidism to have extremely high cholesterol and triglyceride plasma levels. In this instance it is likely that there is a combination of hyperviscosity and atherosclerosis in addition to direct effects of hypothyroidism on cell metabolism.


Perfusion of the brain is strongly influenced by viscosity by the equation blood flow = (C X perfusion pressure X 4d) / (8 x v x l) such that small changes in viscosity produce large decreases in blood flow. Diffuse forebrain signs can result. Viscosity is affected by high molecular weight molecules such as lipoproteins, fibrinogen and immunoglobulins, but also by extremely high cell counts. The most common causes of hyperviscosity in my experience include polycythemia, hyperlipemia and leukaemia. Sometimes polycythemia is a result of hypoxemia and obviously, hypoxemia can also cause diffuse forebrain signs.


Dogs with significant thrombocytopenia can spontaneously bleed into the CNS, causing signs that localize to the site of the haemorrhage. This can occur with no evidence of haemorrhage elsewhere, although this is unusual. Intracranial haemorrhage should be suspected whenever there is acute onset of neurological signs associated with a platelet count of less than 60 x 109/L. A careful physical examination to identify petechiae, ecchymoses and fundic haemorrhages can help to establish the diagnosis. The underlying cause of thrombocytopenia must be researched and treated appropriately.

Bromide toxicity

While bromide toxicity is suspected in animals that are receiving potassium bromide to treat seizures, on occasion it is administered accidentally. Suspicion of bromide intoxication should be raised by a high chloride level in the presence of normal sodium. Typically, affected dogs will have be extremely sedate, often tetraparetic and they tend to have whole body twitches. Measurement of bromide levels will establish the diagnosis.


In summary, a range of different metabolic disorders can produce neurological signs. The most common manifestation is diffuse forebrain dysfunction, but lateralizing signs, focal signs associated with vascular disease and more global signs can also occur.

Further reading

Willard M. Therapeutic approach to chronic electrolyte disorders. Veterinary Clinics of North America Small Animal Practice. 2008;38:535-41

Higgins, MA; Rossmeisl, JH Jr; Panciera, DL. Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005. Journal of Veterinary Internal Medicine. 2006;20:1363-9.

Russell, NJ; Bond, KA et al. Primary hypoparathyroidism in dogs: a retrospective study of 17 cases. Australian Veterinary Journal. 2006;84:285-90.

O'Brien, DP; Kroll, RA et al. Myelinolysis after correction of hyponatremia in two dogs. Journal of Veterinary Internal Medicine. 1994;8:40-8.

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