CASE REPORTS

Hypernatremia in a Cat with Toxoplasma-Induced

Panencephalitis
Christiane Weingart, Dr. med. vet., Achim D. Gruber, Dr. med. vet., PhD, DECVP,
Mathias Brunnberg, Dr. med. vet., DECVS, Barbara Kohn, Dr. med. vet., DECVIM-CA

ABSTRACT
A 12 yr old female neutered Carthusian crossbreed cat was presented due to progressive neurological signs. Clinical
signs included dehydration, stupor, and anisocoria. Laboratory examination revealed severe hypernatremia, azotemia,
hyperglobulinemia, and an erythrocytosis. Clinical signs and hypernatremia suggested an intracranial process. Imaging
studies revealed a loss of structure in the cerebrum, hypothalamus, and pituitary gland. Due to a poor prognosis, the cat
was euthanatized. Histopathological examination revealed a subacute granulomatous and necrotizing panencephalitis
with Toxoplasma-typical protozoa. The Toxoplasma-induced dysfunction of the hypothalamus and pituitary gland led to
diabetes insipidus, which was, in combination with insufficient water intake, the most likely cause for the hypernatremia.
(J Am Anim Hosp Assoc 2016; 52:63–67. DOI 10.5326/JAAHA-MS-6257)

Introduction been dewormed and vaccinated at irregular intervals. For the last 3
Disturbances of the water metabolism associated with hypernatre- wk, the cat had been treated for hyperthyroidism, hypertrophic
mia are rare conditions and can be caused by loss of free water, cardiomyopathy, and hypertension with carbimazole, ramipril, and
hypotonic water loss, or increased intake of sodium. Dependent on amlodipine. Seven days before presentation, total serum T4 was
its severity and on the speed of its development, hyperosmolality within the reference range. For the last 5 days, severe lethargy,
can be life-threatening. The major regulatory hormone responsible inappetence, and hypodipsia had been present. At presentation, the
for fluid homeostasis is vasopressin (antidiuretic hormone), which cat was in lateral recumbency. The body condition score, which
is produced in the hypothalamus and released from the pituitary deteriorated during the last 3 wk, was 1/9. Mucous membranes
gland. Vasopressin deficiency results in diabetes insipidus consist- were dry and pale, the capillary refill time was prompt, and rectal
ing of pure water deficit; a low urine osmolality; and, in the case of temperature was 36.28C. Auscultation of the heart revealed a
reduced water intake hypernatremia, high plasma osmolality and systolic heart murmur (grade II/VI, left side, fifth to sixth
hyperchloremia. This report describes an unusual case of a intercostal space) and a heart rate of 124 beats per min. Pulse
necrotizing panencephalitis involving the hypothalamus and the quality and respiration pattern were normal. The degree of
pituitary gland, presumably causing diabetes insipidus in a cat. dehydration was estimated as 5–6%. Systolic blood pressure was
100 mmHga Neurological examination revealed an abnormal
Case Report mental status with stupor. The palpebral reflex was normal;
A 12 yr old female neutered Carthusian crossbreed cat weighing 1.8 however, the menace response could not be assessed. The pupillary
kg was presented at the Clinic of Small Animals, Freie Universität reflexes were normal, but anisocoria was present. Spinal reflexes
Berlin, Germany due to a 4 mo history of progressive disorientation (femoral nerve, flexor reflexes, carpal extensor) and deep pain
and anisocoria. The cat lived indoors for the entire life and had sensation were normal. The cat was not able to stand without or

From the Department of Veterinary Pathology (A.D.G.) and Clinic of CT, computer tomography
Small Animals (C.W., M.B., B.K.), Freie Universität Berlin, Berlin,
Germany.

Correspondence: weingart.christiane@vetmed.fu-berlin.de (C.W.)

Q 2016 by American Animal Hospital Association JAAHA.ORG 63

 of the azotemia could not be excluded. Serological examination for
TABLE 1 feline leukemia virus antigen and feline immunodeficiency virus
Laboratory Parameters of a 12 Yr Old Cat with Cerebral antibodiesd was negative. The radiological examination of the
Toxoplasmosis and Hypernatremia thorax showed cardiomegaly (vertebral heart score 9.5, reference
Reference range: 6.7–8.1). Ultrasonographic examination of the abdomen was
Day 1 Day 2 Day 3 Day 4 Values unremarkable.
Sodium (mmol/L) 189 184 186 173 145–158 The cat was treated in the intensive care unit. To replace the
Chloride (mmol/L) ND 139 ND 130 110–130 volume deficit, a crystalloid solutionc (sodium content 140 mmol/
Potassium (mmol/L) 4.8 4.6 5.0 5.7 3.6–4.8 L) was administered IV (4.4–5.5 ml/kg/hr). Due to an altered state
Osmolality (mOsm/kg)* 378 368 372 346 290–3201 of consciousness, oral rehydration was not possible. After
Glucose (mmol/L) 9.0 10.7 15.2 13.4 4.5–6.2 rehydration, a mixed infusion of a crystalloid solutione and 5%
Creatinine (lmol/L) 308 188 139 158 53–168 glucosef (1:2 ratio) at a rate of 3.3–4.4 ml/kg/hr was given to replace
Phosphor (mmol/L) ND 3.2 ND 2.4 0.8–1.9 pure water losses. Since the glucose is metabolized, an adminis-
Calcium ionized (mmol/L) 1.1 ND ND ND 0.9–1.4 tration of 5% dextrose solution is equivalent to infusion of water.1
Lactate (mmol/L) 2.4 ND ND ND ,2.5 Vital parameters were measured every hour. After 6 hr, the pulse
ALT (U/L) ND 260 ND ND ,76 rate increased to 168 per min, the respiratory rate ranged from 16
AP (U/L) ND 131 ND ND ,70 to 24 per min, and the blood pressure increased to 140–150 mmHg.
GLDH (U/L) ND 33 ND ND ,6 Initially, electrolyte concentrations were measured every 4–6 hours.
Bilirubin (lmol/L) ND 6.3 ND ND 5 Heating blankets and warming systemsg were used to increase body
Protein (g/L) 74 74 77 76 57–78 temperature. The urine osmolality measured the day after
Albumin (g/L) ND 27 27 26 26–40 admission was 516 mOsm/kg (reference range: 50–3000 mOsm/
Globulin (g/L) ND 47 50 50 ,40 kg).3 The calculated plasma osmolality was 368 mOsm/kg. Within
Hematocrit (l/L) 0.56 0.50 ND 0.42 0.3–0.45 the following 3 days, hydration status and hypernatremia
Leukocytes (G/L) 20 14.4 ND 12.6 6–11 improved, but mild hyperkalemia was detected (Table 1). The cat
Band neutrophils (G/L) 0.4 ND ND ND 0–0.6 was able to lie in sternal recumbency, but was not able to stand.
Segmented neutrophils (G/L) 18 ND ND ND 3–11 Furthermore, the cat was not stupurous, but disoriented and
Eosinophils (G/L) 0.6 ND ND ND 0.6 menace response remained absent. The rectal temperature
Monocytes (G/L) 0.2 ND ND ND 0.04–0.5 increased to 37.48C, but did not return to its reference range
Lymphocytes (G/L) 0.8 ND ND ND 1–4 throughout treatment. At that point of time, the owners agreed to
* 2 perform further diagnostics. On day 4, a computer tomography
calculated: 2 x Na (mmol/L)
ND, not done. (CT) scan of the brain was performed. General anesthesia was
initiated with midazolamh (0.5 mg/kg IV) and propofoli (3 mg/kg)
with assistance and the proprioceptive reflexes with assistance were and maintained with an isoflurane/oxygen mixture after intuba-
absent on all limbs. Based on the neurological examination, a tion. First, a native CT scan of the cranium was carried out using a
central nervous disorder was suspected. Inflammatory, neoplastic, multi-slice spiral CT.j The scan was repeated after administration of
and metabolic/toxic diseases were considered as the most 4 ml contrast agent (300 mg J/ml IV).kk A hypodensity of the brain,
b
important differential diagnoses. Hematological examination especially of the right hemisphere and ventral aspect of the brain,
revealed an erythrocytosis and a mild leukocytosis with a mature including the hypothalamus and pituitary gland, was present
neutrophilia and lymphopenia, consistent with a stress leukogram (Figure 1). After discussing the CT findings with the owner, the cat
c
(Table 1). Biochemistry revealed a severe hypernatremia with a was euthanatized. A complete histopathological examination was
calculated plasma osmolality of 378 mOsm/kg (2 Na [mmol/L], performed. Main findings included a severe subacute; granuloma-
1,2
reference range 290–330 mOsm/kg). Further findings included tous and necrotizing panencephalitis, involving the hypothalamus
hyperchloremia, azotemia, increased liver enzymes, hyperglobulin- and the pituitary gland; and Toxoplasma-typical protozoal cysts
emia, and hyperglycemia. Due to dehydration, a urine sample (bradyzoites). Only a few tachyzoites were found intralesionally
could not be obtained either via cystocentesis nor manual (Figure 2). A further finding was a small (0.6 3 0.4 3 0.3 cm),
expression of the bladder. The clinical findings suggested a prerenal mixed-type meningioma causing pressure atrophy of the paren-
azotemia; however, a renal disease as a primary or additional cause chyma in the caudal lobe of the cortex, but without invasive growth

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 Hypernatremia in a Cat with Panencephalitis

FIGURE 1 (A, B) Computer tomographic examination of the skull of a 12 yr old cat with panencephalitis due to Toxoplasma infection.

or distant metastasis. Due to the small size and the absence of Discussion
invasive growth, it was unlikely that the meningioma was A marked hypernatremia due to a dysfunction of the hypothalamus
responsible for clinical signs. Moreover, a thyroid adenoma, a and the pituitary gland is described in this case report. In patients
biventricular hypertrophy of the myocardium, and a chronic with vasopressin deficiency, normovolemia is maintained by
interstitial nephritis were present. compensatory mechanisms (e.g., increased thirst). At presentation,
the cat described here had progressed to hypovolemic hypernatre-
mia due to insufficient water intake. To the authors’ knowledge,
this complication has not yet been reported in cats infected with
toxoplasmosis. Toxoplasma gondii is a protozoan that occurs
worldwide. It belongs to the Apicomplexa and affects all warm-
blooded animals.4 Cats and other felines are the sole terminal hosts
that produce infectious oocysts via the enteroepithelial cycle. Most
cats develop immunity, which prevents clinical signs. However, cats
can suffer from latent infection and tissue cysts may be present.5
Infection occurs via oral intake of sporulated oocysts, of
Toxoplasma-infected tissue, or congenitally.6 The way of infection
in the cat described here is unclear. Indoor cats are most likely
infected by feeding on raw meat.6 After oral intake of tissue cysts of
infected meat, bradyzoites are released in the gastrointestinal tract
where they multiply in the epithelial cells of the small intestines.
FIGURE 2 Pathohistology of severe subacute necrotizing and After schizogony is completed, gamogony gives rise to oocysts,
granulomatous, partially eosinophilic encephalitis, here of the brain which are excreted with the feces. Oocysts become infectious after
stem region. Lesions included astrocytic proliferations, perivascular having undergone sporulation in the environment. After infection
lymphocytic infiltrations (arrowheads), swelling of empty myelin via intake of oocysts, sporozoites are released in the gastrointestinal
sheaths (asterisk), and removal of debris by vacuolated macrophages tract. The sporozoites divide and form tachyzoites, which penetrate
and microglial cells (arrows). Parasitic cysts consistent with the mucosa and affect internal organs. In cats, the liver, kidneys,
Toxoplasma gondii containing myriads of bradyzoites were present spleen, musculature, lung, heart, eyes, brain, and spinal cord can be
in adjacent brain regions whereas only very few tachyzoites were affected.5–7 Tachyzoites can cause massive tissue damage and
observed in the inflammatory lesions (inset). Hematoxylin and eosin necrosis; in immune-competent individuals, tachyzoites form
stain, bar ¼ 100 microns. PAS reaction, bar ¼ 10 microns (inset). bradyzoites. Bradyzoites divide slowly and cause tissue cyst

JAAHA.ORG 65
development and latent Toxoplasma infections. Clinical signs of hyperaldosteronism as a further cause of hypernatremia typically
toxoplasmosis can be caused by primary infection or reactivation of coincides with severe hypokalemia and, therefore, was unlikely in
a latent infection. Reactivation occurs secondary to immune- this cat. The cat described here most likely developed hypernatremia
suppression in cats suffering from other diseases.8 In the cat due to vasopressin deficiency and a reduced water intake.
presented here, a reactivation of a cerebral toxoplasmosis is likely, Since the chloride transport is linked to sodium, hyperchlor-
since mainly bradyzoites and only a few tachyzoites were present. emia was also present. However, the serum chloride level was not as
Infectious agents were not found in any other organs. The exact severely increased as the sodium concentration. This might be
mechanism of reactivation is not known. Other infectious diseases explained by gastrointestinal losses or a chronic respiratory acidosis
(feline leukemia virus, feline immunodeficiency virus), drugs leading to a compensatory metabolic alkalosis. However, there was
(glucocorticoids, ciclosporin), neoplasias, or stress may precede no vomiting or diarrhea in the history of the cat. The respiratory
6
reactivation. In certain cats, triggering factors cannot be detetced. tract was normal based on auscultation and on radiography. Further
The most important laboratory finding in this cat was marked laboratory abnormalities in this cat included hyperglycemia,
hypernatremia. Sodium concentrations and osmolality of the azotemia, hyperkalemia, hyperphosphatemia, erythrocytosis, in-
extracellular space are regulated by vasopressin. Vasopressin is a creased liver enzymes, hyperglobulinemia, and relative eosinophilia.
hormone that is produced in the hypothalamus and stored in the Hyperglycemia and the persistent lymphopenia despite chronic
caudal lobe of the pituitary gland. If plasma osmolality is increased, antigenic stimulation were indicative for a chronic stress response.
vasopressin causes water retention in the kidney due to production The degree of azotemia was most likely underestimated due to severe
of aquaporins. Deviations in plasma osmolality as low as 1–2% cause muscle atrophy and due to hyperthyroidism. The increased
1
release of vasopressin. Another stimulus for vasopressin release is phosphorus concentration could be due to prerenal or renal disease.
hypovolemia.9 Hypernatremia can occur with hypo-, hyper-, or Moreover, it is described that cats with hyperthyroidism have
normovolemia. Hypovolemic hypernatremia, which is the most hyperphosphatemia as well.12 Aldosterone stimulates the reabsorp-
common cause for increased serum sodium concentrations, is tion of sodium and the excretion of potassium in the distal tubules.
caused by severe renal or gastrointestinal water losses. In the patient Hypernatremia inhibits aldosterone secretion, thus reducing sodium
described here, there was no history of vomiting or diarrhea. Renal reabsorption and increasing the plasma potassium concentration.13
water loss would be a possible cause and may be confirmed by Dehydration may have been the cause for the erythrocytosis and
detection of iso- or hyposthenuric urine. However, initially, urine might have influenced the degree of hypernatremia. Other
was not available for analysis. Rarely, hypernatremia is caused by differential diagnoses for erythrocytosis, which are not likely in this
hypodipsia due to a dysfunction of hypothalamic osmoreceptors case, are chronic hypoxia, inappropriate erythropoietin production,
10,11
inhibiting the thirst mechanism. Hypodipsic hypernatremia has and polycythemia vera. Possible differential diagnoses for the
been described in dogs and cats suffering from intracranial disorders increased liver enzymes in the cat described here were inflammatory
and was a possible contributing pathomechanism in this case. hepatobiliary diseases, neoplasia, hyperthyroidism, and hypoxia due
Normovolemic hypernatremia is caused by free water deficits due to to heart diseases. The hyperglobulinemia and an eosinophil count in
diabetes insipidus. Due to a lack of vasopressin or reduced renal the upper range of normal (relative eosinophilia in a stress situation)
response to vasopressin, an adequate concentration of urine is not were probably related to the toxoplasmosis infection.6,14 Despite
possible. In normovolemic hypernatremia, pure water is lost. hypovolemia, albumin was not increased. Albumin is a negative
Intracellular water flows to the extracellular compartment leading acute phase protein; therefore, in inflammatory disease states, serum
to a constant arterial blood volume. Thus, the patient is albumin concentration will decrease. Further explanations for
normovolemic, as long as the patient has sufficient water intake. hypoalbuminemia in this case were liver failure and renal or
However, dehydration or hypovolemia can develop when water extrarenal losses of albumin.
intake is reduced, which was the case in the cat described here. Hypernatremia causes hyperosmolality of the extracellular
Further potential causes for normovolemic hypernatremia are fever, volume, which causes shrinking of the cells and subsequent neuronal
high environmental temperature, and inadequate access to water.1 dysfunction. Acute hypernatremia can cause clinical signs at sodium
Salt intoxication or the administration of hypertonic sodium concentrations of .160 mmol/L. The signs are related to the rapidity
solutions or sodium bicarbonate may lead to hypervolemic of onset of hypernatremia and include lethargy, tremor, seizures,
hypernatremia with hypertension and lung edema. Based on the coma, or death.1,15–17 In the cat of this report, the clinical signs were
results of the clinical examination and the low blood pressure, most likely caused by hyperosmolality and Toxoplasma-induced
hypervolemic hypernatremia was excluded in this case. Primary panencephalitis. Hypernatremia should be treated with caution and

66 JAAHA | 52:1 Jan/Feb 2016

 Hypernatremia in a Cat with Panencephalitis

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conflicts of interest to declare. 15. Temo K, Rudloff E, Lichtenberger M, et al. Hypernatremia in critically
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KONELAB 30 I; Thermo Clinical Labsystem, Dreieich, Germany 2009;31:E1–E7.
d
Primagnost Duo K; Albrecht GmbH, Aulendorf, Germany 18. Mazzaferro E. Diagnosis and treatment of electrolyte abnormalities. In:
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