March 2017



Signalment (JPC #2137343) Slide A: A 5-year-old cat




HISTOPATHOLOGIC DESCRIPTION: Medulla oblongata and cerebellum: Within the vestibular nuclei and extending into the white matter of the medulla oblongata, there are bilaterally symmetrical areas of rarefaction and hemorrhage measuring up to 2 mm in diameter that are centered upon vessels with fragmented endothelium and surrounded by abundant hyaline material (fibrinoid and necrotizing vasculitis). Within the affected areas there is disruption and vacuolation of the neuropil (spongiosis), with replacement by gliosis, reactive astrocytes, gemistocytes, and cellular debris (necrosis). Neurons are shrunken, hypereosinophilic, with pyknotic nuclei (necrotic) or have dispersion of Nissl substance and a peripheral nucleus (chromatolysis). There are occasional round, swollen, hypereosinophilic axons (spheroids) within dilated myelin sheaths. Vessels are reactive, with hypertrophied endothelial cells, and are surrounded by edema, fibrin, and hemorrhage. Neuronal cell bodies within adjacent, less affected nuclei are pale and swollen (degeneration).


MORPHOLOGIC DIAGNOSIS: Medulla oblongata with vestibular nuclei: Polioencephalomalacia, bilaterally symmetric, marked, with fibrinoid and necrotizing vasculitis, hemorrhage, neuronal necrosis, degeneration and chromatolysis, and gliosis, breed unspecified, feline.


Signalment (JPC #1199288) Slide B: Holstein calf


HISTORY: Six other calves out of 17 were found dead. The calf was prostrate with a temperature of 102.2F when first examined. It had been ill for 10 days with CNS signs and transient diarrhea. After an additional week, it was euthanatized.


HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Multifocally there is marked vacuolation (spongiosis) of both the cortical gray matter and superficial white matter and rarefaction of cortical gray matter in a laminar pattern at the gray-white matter interface, characterized by neuronal necrosis and loss of the neuropil with gliosis, moderate numbers of gitter cells, fewer gemistocytic astrocytes, and abundant edema. There are few dilated, hypereosinophilic axons (spheroids). Vessels within affected areas are often lined by hypertrophied endothelial cells, and cuffed by several many lymphocytes, plasma cells and macrophages which occasionally extend into the surrounding neuropil. The meninges are expanded by clear space (edema) and infiltrated by the previously described inflammatory cells.


MORPHOLOGIC DIAGNOSIS: Cerebrum, cortex: Polioencephalomalacia, cortical, laminar, focally extensive, with neuronal necrosis, edema, spongiosis, and mild lymphoplasmacytic and histiocytic meningoencephalitis, Holstein, bovine.


CAUSE: Thiamine (Vitamin B1) deficiency


ETIOLOGIC DIAGNOSIS: Nutritional polioencephalomalacia


CONDITION: Polioencephalomalacia


SYNONYMS: Chastek paralysis (carnivores)



·      Progressive encephalopathy associated with thiamine deficiency in carnivores (fox, cat, mink) and a less well-established association with thiamine deficiency in young ruminants

·      Thiamine is a dietary requirement of carnivores; deficiency may be caused by:

·      Decreased thiamine intake

·      Consumption of fish containing thiaminase

·      Excessive heating of foods

·      Preservation of meat with sulfur dioxide

·      Upper gastrointestinal disease causing decreased absorption of thiamine

·      Bracken fern and horsetail (Equisetum arvense) are thiaminase containing plants, and will produce thiamine deficiency in horses eating these plants

·      Thiamine is produced in ruminants by microbial synthesis; deficiency may be seen in the very young prior to establishing a functional ruminal flora or in adults caused by:

·      Grain overload and overgrowth of thiaminase-producing bacteria

·      Ingestion of thiaminase-containing plants (bracken fern, horsetails)

·      Ingestion of sulfur and sulfur compounds

·      Associated with cobalt deficiency, molasses, and high urea diets

·      Liver and muscle are primary sites of thiamine storage



·      Phosphorylated thiamine is the coenzyme cocarboxylase, which is involved in oxidative decarboxylation reactions throughout the body

·      Cocarboxylase is a cofactor for: Transketolase, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase and branched-chain alpha-keto acid dehydrogenase

·      Transketolase is utilized in the hexose monophosphate shunt, is active in the white matter and is important in the metabolism of oligodendrocytes

·      The exact pathogenesis is unknown; however, the following factors are believed to play a role:

·      Free-radical injury to the blood-brain barrier > vacuolation of neuropil

·      Degenerative changes in glia > rupture > increased extracellular space > vascular dilation

·      Decreased transketolase activity > decreased glucose utilization > metabolic burst > production of lactic acid > focal lesions

·      Activity of ATP-dependent sodium and water transport mechanisms in neurons is reduced leading to intraneuronal swelling, elevated intracranial pressure, and necrosis of neurons

·      Ruminants: Increased sulfur intake > sulfate reduced to sulfite > sulfite cleaves thiamine into pyrimidine and thiazole

·      Neurons in mid to deep lamina of parietooccipital lobes are preferentially affected.



·      Transient diarrhea before onset of neural signs

·      Abrupt onset of depression, muscle tremors, cortical blindness

·      Ventriflexion of neck in carnivores

·      Ataxia progressing to recumbency with opisthotonus, teeth grinding, nystagmus, and extensor rigidity

·      Thiamine deficiency is always attended by elevation of blood pyruvate



·      Carnivores: lesions pass through the sequence of vacuolation > vascular dilation > hemorrhage > necrosis

·      Lesions are in areas of vulnerability, primarily periventricular grey matter and occasionally the middle laminae of the occipital and temporal cortex; more specifically, the inferior colliculi and the medial, red, and lateral geniculate nuclei are affected

·      Petecchial hemorrhages, bilaterally symmetrical in brain stem nuclei, most often the caudal colliculi and other paraventricular nuclei; often grossly visible in colliculi and vestibular nuclei

·      May see myocardial degeneration and necrosis that is more prominent in the right versus the left ventricle

·      Ruminants: Swollen cerebrum; flattened gyri; narrow sulci; prominent cerebral cortical necrosis with unaffected cerebellar cortex; cerebral cortical atrophy; rare tentorial herniation and coning of the cerebellum in severe cases

·      Yellow discoloration of cerebrocortical gray matter; affected areas autofluoresce under ultraviolet light; possible due to ceroid-lipofuscin or mitochondrial ATP synthase.

·      Hydrocephalus ex vacuo occurs in long term cases



·      Carnivores: Caudal colliculi most consistently affected

·      Initial change is vacuolation in nuclei of special susceptibility (lateral geniculate bodies, caudal colliculi, red nuclei)

·      Vacuolation of neuropil (status spongiosis), vascular dilation, endothelial hypertrophy, edema, and hemorrhage (often terminal event)

·      Gliosis and neuronal necrosis

·      Recovered animals develop intense astrogliosis in affected areas

·      Ruminants: Marked laminar cerebral cortical necrosis

·      Degeneration and necrosis of neurons of the middle to deep cortical laminae

·      Infiltration by moderate numbers of macrophages in necrotic areas

·      Laminar pattern of cerebral cortical edema and necrosis; astrocyte swelling

·      In advanced cases with prolonged survival, areas of marked atrophy of cerebral gyri with attenuated or absent gray matter zone



·      Response to injectable thiamine

·      Rumenal gas elevation for sulfur

·      Elevated blood pyruvate; decreased erythrocytic transketolase activity



·      Microscopic differentials for laminar necrosis in ruminants:

·      Lead poisoning: basophilic stippling of RBCs, intranuclear inclusions in renal tubular epithelia, hepatocytes and osteoclasts

·      Salt toxicity: circumstantial in ruminants but well established in pigs

·      Hypoxia

·      Sulfur toxicity: high sulfur intake



·      Horse: Bracken fern and horsetail (Equisetum arvense) are thiaminase containing plants

·      Other encephalomalacias in equine include:

·      Leukoencephalomalacia (moldy corn disease): Fumonisin B1 from Fusarium verticillioides (F. moniliforme) and F. proliferatum results in necrosis of white matter of the cerebral hemispheres

·      Nigropallidal encephalomalacia: Yellow star thistle ingestion causes malacia of pallidus and substantia nigra

·      Swine: Salt toxicity or water deprivation: Laminar necrosis with infiltrate of eosinophils

·      Man: Wernicke’s encephalopathy, due to thiamine deficiency results in symmetric paraventricular malacia of the gray matter

·      Sled dogs encephalopathy: thalamic necrosis

·      Small breed dogs (pug, Yorkies, maltese, shihtzu, Chihuahua): Necrotizing meningoencephalitis or granulomatous meningoencephalitis; unilateral

·      Cats: Leukoencephalomyelopathy by feeding a gamma-irradiated dry diet with elevated peroxide and reduced vitamin A concentrations

·      Aquatic animals: Higher susceptibility due to fish-based diet that may contain thiaminase (especially smelt)

·      Ataxia with white matter degeneration is reported in lions, cheetahs, cats, English Foxhounds, Landrace-cross pigs, rats, and nonhuman primates where deficiencies in vitamins A, B12 (cobalamin),B3 (nicotinamide),B6 (pyridoxine),

and B1 (thiamine) have been implicated



1.    Anholt H, Himsworth C, Britton A. Polioencephalomalacia and heart failure secondary to presumptive thiamine deficiency, hepatic lipidosis, and starvation in 2 abandoned Siamese cats. Vet Pathol. 2016 Jul;53(4):840-3.

2.    Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:309-314.

3.    Caulfield CD, Kelly JP, Jones BR, Worrall S, Conlon L, Palmar AC, and Cassidy JP. The experimental induction of leukoencephalomyelopathy in cats. Vet Pathol. 2009;46:1258–1269.

4.    Croft L, Napoli E, et al. Clinical evaluation and biochemical analysis of thiamine deficiency in Pacific harbor seals (Phoca vitulina) maintained at a zoological facility. J Am Vet Med Assoc. 2013 Oct 15:243(8):1179-89.

5.    Jones TC, Hunt RD, King NW. Veterinary Pathology. 6th ed. Baltimore, MD: Williams and Wilkins; 1997: 794-795.

6.    Loneragan GH, Gould DH, Callan RJ, Sigurdson CJ, Hamar DW. Association of excess sulfur intake and an increase in hydrogen sulfide concentrations in the ruminal gas cap of recently weaned beef calves with polioencephalomalacia. J Am Vet Med Assoc. 1998;213:1599-1604.

7.    Markovich JE, Freeman LM, Heinze CR. Analysis of thiamine concentrations in commercial canned foods formulated for cats. J Am Vet Med Assoc. 2014 Jan 15;244(2):175-9.

8.    Markovich JE, Heinze CR, Freeman LM. Thiamine deficiency in dogs and cats. J Am Vet Med Assoc. 2013 Sep 1;243(5):649-56.

9.    Miller AD, Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:885-893.

10.  Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby-Year Book Inc.; 1995:277-2801.

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