Clinical and MRI findings of hemorrhagic infarcts in two cats with positive outcomes

Abstract

Case series summary

A 1.5-year-old male neutered domestic shorthair cat presented with an acute onset of lethargy and difficulty jumping. Prior medical history included a restrictive perimembranous ventricular septal defect and mild mitral regurgitation. Neurologic examination showed left hemiparesis and absent menace in the left eye. MRI revealed a lesion in the right frontal lobe and caudate nucleus with intralesional hemorrhage and restricted diffusion consistent with hemorrhagic infarct. A 6-year-old male neutered domestic shorthair cat presented with three neurologic episodes over 3 months, one consisting of circling to the right, absent menace in the right eye and right-sided postural reaction deficits, and the other two consisting of vestibular signs. MRI revealed a chronic hemorrhagic infarct of the left caudate nucleus. Both cats demonstrated favorable recovery, with cat 2 experiencing a fourth event 9 months after MRI.

Relevance and novel information

This case series details the first two cases of feline hemorrhagic infarct with ante-mortem diagnosis, MRI findings and recovery with a good long-term outcome. Hemorrhagic infarcts, uncommonly reported in companion animals, are a subtype of stroke involving hemorrhage resulting from reperfusion or collateral circulation into an ischemic area of brain tissue. This report discusses typical MRI findings in humans, including differentiation from intracerebral hemorrhage, and the potential role of comorbidities on the development and outcome of hemorrhagic infarcts in cats.

Introduction

Cerebrovascular disease (CVD) is any abnormality of the brain resulting from pathology affecting its blood supply.^{1 –4} The clinical manifestation of CVD are strokes, which are now being reported regularly in companion animals.^{1 –3} Strokes can be hemorrhagic or ischemic. Intracerebral hemorrhage (ICH) or a hemorrhagic stroke is caused by coagulopathy or rupture of a blood vessel and subsequent development of a mass of blood in the brain.^1,2,4 Ischemic strokes (ISs) are caused by occlusion of a blood vessel leading to ischemia and infarction of the brain tissue.^1,2,4,5 Most infarcts are ischemic; however, some can undergo hemorrhagic transformation (HT) resulting in a hemorrhagic infarct (HI).^1,4,6 This occurs when blood flow is re-established through the affected vessel or collateral circulation, and because of damage to the vessel walls, blood leaks into the ischemic brain tissue.^{4 –6}

This is the first paper to describe the clinical presentation, MRI findings and documented recovery in cats with HI.

Case series description

Case 1

A 1.5-year-old male neutered domestic shorthair cat, presented with an approximately 18 h history of lethargy, reduced playfulness and difficulty jumping. Prior medical history included a restrictive perimembranous ventricular septal defect and trivial mitral regurgitation. Physical examination revealed a grade III/VI systolic heart murmur. Neurologic examination abnormalities included absent menace response in the left eye, left-sided hemiparesis with spontaneous knuckling and decreased postural reactions in the left thoracic and pelvic limbs. The primary differential diagnoses included infectious or non-infectious meningoencephalitis, congenital anomaly, vascular event or neoplasia. Blood pressure was 150 mmHg. No relevant findings were identified on a serum chemistry panel. Complete blood count (CBC), total thyroxine (T4) and urinalysis were normal. Two days after initial presentation, the cat was anesthetized and an MRI examination (Optima 1.5T; GE) of the brain was performed. Sequences included sagittal and transverse T2-weighted fast-spin echo (T2W), transverse T1-weighted fast-spin echo (T1W), fluid-attenuated inversion recovery (FLAIR), T2*-weighted angiography (SWAN), diffusion-weighted imaging (DWI), T1W post-contrast with fat saturation and T1W post-contrast in sagittal, dorsal and transverse planes. A round mass-like lesion involving the right frontal lobe and caudate nucleus was identified (Figure 1).

Figure 1

Hemorrhagic infarct (arrows) within the right frontal lobe and caudate nucleus of cat 1. Left caudate nucleus (asterisk) is identified for anatomic reference. (a) Transverse T2-weighted fast-spin echo (T2W) image reveals a hyperintense lesion with a central area of isointensity (arrowhead). (b) Transverse T2*-weighted angiography image shows a large susceptibility artifact consistent with hemorrhage. (c) Transverse T1-weighted fast-spin echo (T1W) image shows the lesion is primarily isointense but with foci of hyperintensity (arrowhead). The lesion is mild to moderately, heterogeneously contrast enhancing with a faint ring enhancement pattern on (d) T1W post-contrast imaging. The lesion is hyperintense on (e) diffusion-weighted imaging with (f) reduced apparent diffusion coefficient values indicating restricted diffusion typical of an infarct

The mass was T2W and FLAIR hyperintense with a central area of isointensity, primarily T1W isointense with some hyperintense foci, and had mild to moderate, heterogeneous contrast enhancement with a faint ring enhancement pattern on T1W post-contrast imaging. The lesion was associated with a susceptibility artifact on SWAN, consistent with hemorrhage, and was hyperintense on DWI with reduced apparent diffusion coefficient (ADC) values indicating restricted diffusion typical of an infarct. These findings were consistent with a hemorrhagic infarct. Cerebrospinal fluid analysis revealed normal total nucleated cell count (1 cell/µl) and normal total protein (13 mg/dl) with a slight increase in the proportion of neutrophils on cytology consistent with a stroke. The cat was discharged after the MRI and was reported by the owner to be doing well, with no reported neurologic issues 9 months after presentation.

Case 2

A 6-year-old male neutered domestic shorthair cat, presented with a history of three separate, acute onset, spontaneously resolving neurologic episodes over a 3-month period. There was no significant prior medical history. The first neurologic episode consisted of acute onset abnormal mentation, compulsive circling to the right and hyporexia. Neurologic examination findings at that time included absent menace response in the right eye, mild anisocoria (right eye more mydriatic than the left eye) with normal pupillary light reflexes, and delayed proprioceptive placing in the right forelimb and right pelvic limb. The second episode, occurring 2 months later, consisted of peracute onset loss of balance. Neurologic examination revealed a subtle right-sided head tilt with slight positional ventral strabismus in the right eye. No relevant abnormalities were identified on a serum chemistry panel performed at the time of each of the first two episodes; CBC and T4 were normal. Blood pressure at the time of the second episode was in the range of 138–142 mmHg. Given the acute onset of signs with spontaneous resolution, the primary differential diagnosis was recurrent vascular events. After the second event, clopidogrel was administered (3.8 mg/kg PO q24h) as an empiric, prophylactic therapy owing to recurrent episodes. The third episode, occurring 2 weeks later, consisted of peracute onset of ataxia and loss of balance with rapid spontaneous resolution of signs. The cat was presented 1 week after the third episode for MRI. Neurologic examination at that time was normal. MRI of the brain (Figure 2), performed using the same study protocol as in case 1, revealed asymmetry of the caudate nuclei and lateral ventricles – the left caudate nucleus appeared smaller and the left lateral ventricle was larger compared with the right side. A focal lesion was identified in the dorsolateral head of the left caudate nucleus. This lesion was primarily isointense on T2W and FLAIR images, with a hyperintense rim. It appeared isointense on T1W images, showed moderate and homogeneous contrast enhancement, and was associated with a susceptibility artifact on SWAN. The lesion was not appreciable on DWI.

Figure 2

Chronic hemorrhagic infarct (arrows) within the left caudate nucleus, which is smaller than the right caudate nucleus (asterisk) and associated with an enlarged left lateral ventricle (arrowheads). (a) Transverse T2-weighted fast-spin echo and (b) fluid-attenuated inversion recovery images reveal a lesion that is primarily isointense with a hyperintense rim. (c) Transverse T2*-weighted angiography image shows a susceptibility artifact consistent with hemorrhage. (d) The lesion demonstrates moderate contrast enhancement on T1-weighted fast-spin echo post-contrast imaging. The lesion is not visible on (e) diffusion-weighted imaging or (f) apparent diffusion coefficient map

These findings were most consistent with a chronic hemorrhagic infarct with resulting atrophy of the left caudate nucleus. The cat was discharged after the MRI. Nine months after the third episode, the cat had a fourth acute onset vestibular event that spontaneously im-proved over several weeks. No further episodes have been reported since.

Discussion

To the authors’ knowledge, this report describes the first two cases of feline HI with MRI findings and positive outcomes. HI is an uncommon type of stroke in dogs and cats with an unknown prevalence, although a recent study on ISs in dogs was noted to exclude 18/219 identified IS cases from data analysis because of the presence of hemorrhage within the infarct. ⁷ In humans, approximately 15–43% of cerebral infarcts are complicated by hemorrhage. ⁶ In general, data on CVD in cats is sparse, even more so regarding HI. In the largest study describing CVD in 16 cats, five had HIs, all diagnosed post mortem. ⁴ Subsequent reports of ISs in cats have not documented any cases of HI.^8,9

The diagnosis of HI was made in these two cases based on clinical history consistent with a stroke and available MRI descriptions in dogs and humans.^5,6,10,11 One of the challenges in diagnosing HI on imaging is distinguishing it from ICH. ¹⁰ This distinction is im-portant for identifying predisposing factors, developing appropriate therapeutic plans and prognostication. Although gradient echo or SWAN sequences are excellent in detecting hemorrhagic lesions – owing to susceptibility artifacts caused by the paramagnetic properties of iron in blood they do not reveal the underlying cause of the hemorrhage. The appearance of the hemorrhagic lesions on T1W and T2W images varies depending on the age of the hemorrhage and the stage of hemoglobin degradation (Table 1).^1,2,5

Table 1

MRI appearance of hemorrhage on T1-weighted fast spin echo (T1W) and T2-weighted (T2W) fast-spin echo sequences based on the breakdown of hemoglobin (Hb) over time^1,2,5

Stage	T1W	T2W	Hb breakdown product
Hyperacute (<24 h)	Isointense	Hyperintense	Oxyhemoglobin
Acute (1–3 days)	Isointense	Hypointense	Deoxyhemoglobin
Early subacute (>3 days)	Hyperintense	Hypointense	Intracellular methemoglobin
Late subacute (>7 days)	Hyperintense	Hyperintense	Extracellular methemoglobin
Chronic (>14 days)	Hypointense	Hypointense	Hemosiderin

However, unlike in ICH, DWI of HI will reveal the presence of discrete regions of restricted diffusion remote from the hemorrhagic area indicative of ischemia; this finding was seen in case 1.^6,10,12 Importantly, although ADC values are reduced in the early stages of ischemic stroke, they return to normal over time and may subsequently increase as the stroke evolves.^2,6,5,12,13 This may account for the lack of ADC abnormalities in case 2, for which other MRI findings, in conjunction with clinical history, suggest a chronic infarct. In this case, the location of the HI in the caudate nucleus is most consistent with the clinical signs reported in the first neurologic episode, which occurred approximately 3 months before MRI. In addition, chronicity of the lesion would explain the small size of the caudate nucleus and enlargement of the lateral ventricle resulting from cell and axonal loss and possible damage to the ependymal lining, respect-ively. ¹³ In humans, magnetic resonance angiography and perfusion-weighted imaging can also be useful in diagnosing HI; these techniques are yet to be widely used in veterinary medicine. ¹⁰

Another useful factor to distinguish between HI and ICH is the location of the lesion. In humans, ICH involving the caudate nucleus is uncommon. ¹⁰ However, with HI there is a predilection for basal ganglia, including the caudate nucleus, and deep cortical tissue.^6,10 Interestingly, this predilection aligns with our two cases, which involved lesions in the caudate nuclei, but differs from previously reported cases where 4/5 cats had HI confined to the brainstem and the fifth had multifocal lesions affecting both the cerebrum and brainstem. ⁴

Both cases reported here survived the acute HI, in contrast to the previously reported poor prognosis in five cats. ⁴ There are no data regarding the impact of comorbidities on short- or long-term outcome in HI in dogs or cats or in cat CVD in general. Studies including dogs with IS conflict with earlier studies reporting shorter survival times and increased risk of recurrence in dogs with identifiable comorbidities. ¹⁴ However, a recent publication suggests there is no significant difference. ⁷ It is possible that the poor prognosis of previously reported cases of feline HI is related to the identified comorbidities (hepatic lipidosis or hepatitis in four cats; hepatic lipid-osis, hyperthyroidism and nephritis in one cat), which was not identified in case 2. ⁴ Case 1 did have pre-existing cardiac disease. Although cardiomyopathy has been associated with an increased risk of thromboembolic disease in cats and was reported as a predisposing factor for IS in one cat, the significance of the cardiac disease in case 1 is unknown.^3,4 It is also worth noting that additional testing may have led to the discovery of relevant comorbidities; such testing includes urine protein:creatinine ratio, abdominal ultrasound and coagulation assessment (prothrombin time, partial thromboplastin time, visoelastic coagulation monitoring or thromboelastography).

Although no studies have compared the prognosis and survival between HI and IS in dogs or cats, the overall prognosis for IS is considered good, with recovery commonly reported after supportive care alone.^3,7 In two reports describing ischemic strokes in cats, all cats survived the acute event.^8,9 In humans, there is some dis-agreement about whether HT worsens outcomes in IS. Some studies report increased morbidity and mortality associated with HT, while others find no significant difference – or even suggest a more favorable early outcome – possibly due to improved reperfusion of ischemic tissue.^15,16

Conclusions

To the authors’ knowledge, these are the first reported cases of HI in cats that include detailed clinical and MRI findings. Both cats had HI lesions in the caudate nuclei, with no clear predisposing cause identified. MRI findings were comparable with those reported in human cases. Both cats recovered spontaneously, although one experienced a subsequent neurologic event presumed to be another stroke.