A 1.25 year old, male-neutered Chihuahua was presented with a four-day history of lethargy, decreased appetite, and tachypnea. He was regularly dewormed and vaccinated. In the general examination, the dog showed mild apathy and generalized high-frequency, low-amplitude tremor. Rectal body temperature was 38.7 C. Breathing pattern was normal, frequency was 32/min with physiological effort. Auscultation was inconclusive due to whole body tremor. Coughing and retching was provoked when palpating the larynx. On cardiac auscultation the heartbeat was regular with 120 beats per minute (bpm), no heart murmur was audible. Femoral pulses bilaterally were strong, regular, and synchronous with heart beat. Capillary refill time was under 2 s, the mucous membranes were pale-pink and moist. Peripheral lymph nodes were non-painful, soft and under 1cm in diameter on palpation. Abdominal palpation revealed no abnormal intraabdominal structures and no signs of pain. Mild serous ocular discharge in both medial canthus was noted without any other ocular abnormalities. Macroscopical evaluation of external ears, nose, and skin were unremarkable. Gait and posture were normal. At this timepoint, a neurological examination was not performed due to the lack of obvious involvement of the nervous system on general examination. Complete blood count, clinical chemistry, serum electrolytes, and abdominal ultrasonography were without clinically relevant abnormalities. The owner declined thoracic radiographs at this time point and decided for further outpatient therapy with non-steroidal anti-inflammatory and antibiotic medication. At home, 12 h after first presentation in the clinic, the dog developed generalized tonic-clonic seizure. The seizure had lasted for more than 2 h before the dog was presented to the emergency service again. The dog showed tonic-clonic movements, impaired consciousness, salivation, and a gurgling laryngeal stridor during in- and expiration. Body temperature was measured at 42 C, the heart rate was 162 bpm, no heart murmur was audible. Femoral pulses were strong bilaterally, regular, and synchronous with the heartbeat. Breathing frequency was 52/min. Capillary refill time was under 2 s, the mucous membranes were pale-pink and moist. The dog had brown-reddish diarrhea. Neurologic examination revealed generalized tonic-clonic seizure while the dog was in lateral recumbency. Menace response was absent in both eyes. The dog showed no facial paralysis and an increased tone of the masticatory muscles. Pupillary light reflex, gagging, strabismus, vestibulooccular reflexes, facial sensation, pain sensation and spinal reflexes were not evaluable due to ongoing seizure. The dog was stabilized with diazepam (4 x 2 mg/kg i.v., Diazepam Lipuro, B.Braun, Melsung, Germany) and phenobarbital (2 x 2 mg/kg i.v., Luminal, Desitin, Hamburg, Germany) and resuscitative fluid therapy (20 ml/kg/h for 3 x 20 min as bolus infusion, Sterofundin ISO Vetcare, B.Braun, Melsung, Germany) followed by continuous rate infusion (3 ml/kg/h, Sterofundin BG-5, B.Braun, Melsung, Germany). Thoracic radiographs were unremarkable. After cardiovascular stabilization and treatment of seizures leading to their interruption, neurological examination showed coma, bilateral non-responsive miotic pupils, and generalized absent cranial reflexes, while the breathing pattern remained normal, why a severe brainstem lesion with primary forebrain disease was suspected. Due to a grave prognosis, the owners elected for euthanasia.
Post mortem MRI (Figure 1) showed generalized swelling of the gray matter in the cerebrum and cerebellum with secondary flattening of gyri and sulci. Cortical gray matter displayed increased signal in T2w and FLAIR and decreased signal in T1w. The boundary between subcortical white matter and cortical gray matter was mostly blurry in all sequences. Caudal brainstem and cerebellum showed multifocal, intraaxial, small, round lesions with signal void in T2w and T1w. The fourth ventricle and cisterna magna were filled with material causing signal void in T2w and T1w without significant mass effect.
Examination of CSF sampled post mortem atlanto-occipitally revealed severely elevated number of erythrocytes without signs of erythrophagocytosis. Leukocyte value was elevated, the exact number was not countable. Protein content measured 188 mg/dl (reference values <25 mg/dl). Cell differentiation showed 91% lymphocytes, 7% monocytes and 2% neutrophils.
At necropsy, a moderate flattening of the gyri and narrowing of sulci of the brain (Figure 2A) was observed in conformity with the MRI results and interpreted as edema. In addition, mild cerebellar vermal herniation into the foramen occipitale magnum was visible. The meningeal vessels were moderately and diffusely congested. The dog had hemorrhagic intestinal content and a single nematode was found in the small intestine. Histopathologicallly, the gray matter of the cerebrum as well as the cerebellum showed moderate, multifocal, non-symmetrical, lympho-plasma-histiocytic, necrotizing inflammation. Inflammatory cell infiltrates were mainly found in the perivascular space. Furthermore, primarily small to medium sized blood vessels in the gray matter and especially prominent in the leptomeninx displayed loss of integrity of the vascular wall with moderate to severe infiltration with partially degenerated lymphocytes and macrophages resembling vasculitis of the leukocytoclastic type (Figure 2B). The spinal cord did not show any morphological changes.
IHC of selected sections of the CNS revealed infiltration of a moderate to high number of CD3-positive T-lymphocytes, low to moderate number of CD204-positive macrophages and few CD20-positive B-lymphocytes, respectively, in the partially destructed vascular wall and the perivascular space (Figures 2C-E). Using IHC and histochemistry, no infectious agent or signs of demyelination were detected.
In addition, mild, mucosal hemorrhages and few dilated crypts and mild flattening of villi were observed in the small intestine. Due to the macroscopic and histological lesion in the small intestine, parvovirus infection was ruled out by IHC. The spleen showed moderate lymphoid depletion. In the lung only moderate, diffuse, acute alveolar edema and hyperemia were found. These changes were interpreted as having developed during agony. No signs of parasites, e.g. Angiostrongylus vasorum, were found in the lungs, heart, gastrointestinal tract, or CNS via gross and microscopic examination. The remaining investigated tissues lacked significant microscopic lesions.