Suspected spontaneous early hemorrhagic transformation of multiple ischemic strokes secondary to primary splenic torsion in a German Shepherd dog

1.1 Clinical presentation

A 3-year-old female German Shepherd dog was presented with acute onset of intracranial clinical signs. The owner reported food-responsive enteropathy for 2 years associated with poor body condition. Six days before presentation, the dog was weak and had lost its appetite for 2 days without any apparent reason. The day before presentation, the dog experienced a brief generalized tonic-clonic epileptic seizure (GTCS) with hypersalivation. The next day, the owner described sudden deterioration in neurological condition with right lateral decubitus, right-sided head tilt, pathological nystagmus that changed direction depending on the position of the head, and spasticity of all 4 limbs. The left lateral decubitus position was not tolerated by the dog. There was no history of trauma or toxin exposure. Physical examination disclosed only bradycardia and low body condition score (3/9). Neurological examination identified stupor, opisthotonus, extensor rigidity of the thoracic limbs with pelvic limbs held in extension and flexed at the hips and consistent with decerebellate posture, crossed extensor reflexes in the 4 limbs, positional vertical nystagmus, absence of menace response in the right eye but normal palpebral reflex on both sides, loss of sensitivity of the right nostril, and anisocoria with left-sided myosis. Postural reactions and vision could not be assessed because of agitation. The clinical signs were consistent with acute multifocal encephalopathy, including thalamocortical sign (GTCS), right-sided rostral myelencephalon or left-sided caudal cerebellum (right-sided central vestibular syndrome), and right trigeminal nerve dysfunction or left thalamocortical sign (loss of sensitivity of the right nostril). Intracranial hypertension (ICHT) was suspected based on the presence of stupor and bradycardia. Absent menace response in the right eye was consistent with a left-sided cerebral cortical or cerebellar lesion. Left-sided myosis was considered as partial Horner's syndrome consistent with a left-sided thalamic or brainstem lesion. Differential diagnoses included an inflammatory or vascular process or, less likely, a neoplasm or metabolic or toxic encephalopathy.

1.2 Investigations

Systolic arterial blood pressure was 200 mm Hg, which was consistent with the suspicion of ICHT. Routine blood gas analysis, serum biochemistry, and urinalysis results were within reference intervals (RI). A CB disclosed mild anemia (PCV, 24%; RI, 35%-52%; hemoglobin, 8.2 g/dL; RI, 12.4-19.2 g/dL) and monocytosis (2680/μL; RI, 400-1600/μL). Platelet count was within the RI (526 K/μL; RI, 64-613 K/μL). High-field magnetic resonance imaging (MRI; Signa HD23 optima 1.5T; General Electric Healthcare) of the brain included T2-weighted fast recovery fast-spin echo (T2W), T1-weighted fast-spin echo (T1W), T2W fluid-attenuated inversion recovery (T2 FLAIR), T2W with fat suppression (T2W FS), T2 star-weighted angiography (SWAN), diffusion-weighted imaging (DWI) with b = 1000, and precontrast and postcontrast 3-dimensional fast spin echo (CUBE) T1W with fat suppression (T1W FS) sequences. Gadoteric acid was administered IV (0.1 mmol/kg). All intensities were compared with those of normal gray matter for descriptive purposes. Six small focal T2W and T2 FLAIR hyperintense lesions were observed within the left and right thalami, right side of the mesencephalon, left side of the myelencephalon, and both sides of the spinal cord at the level of C1 (Figure 1). In these areas, lesions were isointense to hypointense on T1W and hyperintense on DWI and SWAN images, and apparent diffusion coefficient (ADC) maps did not identify any abnormalities. The left thalamic lesion showed mild contrast enhancement (Figure 2). These lesions were suspected to represent acute lacunar ischemic stroke (IS) in the distribution of the proximal perforating arteries (thalamus), caudal perforating arteries (mesencephalon), and vertebral arteries (myelencephalon, spinal cord). Two T1W hypointense and T2W isointense to hyperintense lesions with T2W and T2 FLAIR hyperintense peripheral rims (perilesional edema) were observed within the right rostral cerebellar hemisphere (Figures 1 and 3) and the right rostral colliculus. These lesions were associated with strong susceptibility artifacts on SWAN and were hypointense on the DWI and ADC maps. They measured respectively 16 × 12 × 8 mm and 5 × 2 × 2 mm. These lesions were suspected to represent hemorrhagic stroke (HS) in the distribution of the right rostral cerebellar artery and perforating arteries, respectively. The differential diagnosis for multiple IS includes hypercoagulable states, systemic hypertension, neoplasia, heartworm disease, ceroid amyloid angiopathy, and septic disease.^1-8 The differential diagnosis for multiple nontraumatic intraparenchymal HS includes primary causes, such as systemic hypertension and ceroid amyloid angiopathy, and secondary causes, such as vascular malformations, intracranial neoplasms, endoparasitism (Angiostrongylus vasorum), and coagulopathy.^{3, 5, 7, 9, 10} The right temporal muscle showed a focal area of T2W hyperintensity and increased contrast enhancement consistent with a contusion secondary to GTCS or, less likely, focal inflammation or necrosis.

To evaluate the underlying cause of IS and HS, thoracic and abdominal computed tomography CT (BrightSpeed S 16 slices; General Electric Healthcare) scans were obtained after MRI. Thoracic imaging did not identify any abnormalities. Abdominal images showed generalized splenomegaly with a spiral-shaped pedicle with a whirl sign and lack of contrast enhancement of the splenic parenchyma. This lesion was consistent with splenic torsion, which was confirmed by ultrasonography using color Doppler examination (Affiniti 50G; Philips Medical Systems; Figure 4). The differential diagnoses included primary torsion and trauma (unobserved). Computed tomography also disclosed multiple wedge-shaped hypoattenuating and hypoenhancing areas within the renal cortex and medulla consistent with infarcts (Figure 5), right renal hypoplasia, a small volume of peritoneal effusion, and mild mesenteric lymphadenomegaly. Peritoneal fluid analysis was consistent with aseptic peritonitis, presumably secondary to splenic torsion.

Cerebrospinal fluid (CSF) analysis after cerebellomedullary cisternal collection showed a marked increase in total protein concentration (1.29 g/L; RI, 0-0.25 g/L) and total nucleated cell count (TNCC; 310/μL; RI, 0-5/μL) with neutrophilic pleocytosis (78%), erythrophagocytosis, and monocytic activation. The potential for blood contamination was low (40 erythrocytes/μL). Cerebrospinal fluid culture was negative.

Ancillary tests including prothrombin time, activated partial thromboplastin time, antithrombin III activity, and serodiagnosis (A. vasorum immunoassay; Leptospira spp. microscopic agglutination tests; Ehrlichia canis, Borrelia burgdorferi, and Anaplasma phagocytophilum/platys ELISA) were within RI. Polymerase chain reaction testing for Babesia spp., Ehrlichia spp., Anaplasma spp., and Hepatozoon canis yielded negative results.

1.3 Treatments

The dog initially was stabilized with repeated boluses of mannitol (1 g/kg IV), phenobarbital at a loading dose of 21 mg/kg IV over 24 hours and then 5 mg/kg IV q12h as well as fluid therapy. After MRI, CT, and CSF collection, corticosteroid treatment was initiated with prednisolone (0.5 mg/kg PO q24h) for brain edema. As soon as neurological condition was stable, laparotomy confirmed splenic torsion and disclosed entrapment of the left pancreatic limb by the spleen. Splenectomy, partial pancreatectomy of the left limb, and preventive incisional gastropexy also were performed. The histology of the spleen was consistent with hemorrhagic infarction. After surgery, intensive physical rehabilitation was initiated. Phenobarbital was continued PO at the same dosage. Ampicillin/sulbactam (20 mg/kg PO q12h) was initiated for 2 weeks. Corticosteroid treatment was tapered progressively over 3 weeks.

1.4 Outcome

Noninvasive blood pressure was measured daily for 1 week and remained within the RI. The PCV rapidly normalized to approximately 34%. Neurological status progressively improved, and sternal decubitus was supported after 1 week. Conscious proprioceptive testing was normal in the left limbs within a few days. Postural reactions were present in the right limbs 10 days after presentation. The dog was able to stand within 12 days and walk alone within 17 days, with severe right hemiparesis. After 6 weeks, the dog was able to walk and run with persistent ataxia in all 4 limbs, more marked in the right limbs, and had right positional ventrolateral strabismus. Three months after presentation, the clinical examination was normal, and slight ataxia was only noticed in the right limbs.