Brain ischemic stroke is a leading cause of death that is caused by occlusion of the brain arteries. Nowadays the main focus of stroke treatment is on reducing the time of treatment and differentiation between the “core infarction” and “pre-infarction ischemia penumbra” because patients with a large area of peri-fraction ischemia benefit most from the thrombolysis and intra-arterial thrombectomy (
1). Application of CT perfusion has increased in the recent years for evaluation of acute ischemia and differentiation between the core infarction and peri- infarction ischemia, but its application is not standard of care because of controversies about standard protocol and its effect on patients’ prognosis. The main physiologic parameters evaluated by CT perfusion are CBF, CBV and MTT. Areas with markedly decreased CBV/CBF are considered as infarction and the area with increased MTT and relatively preserved CBV or even slightly increased CBV is considered as “peri-infarction ischemic penumbra”. The patients with large pre-infarction ischemia can benefit from thrombolysis and intra-arterial thrombectomy. Generally, patients with relatively small ischemia penumbra do not benefit from thrombolysis/ thrombectomy and may just suffer from the treatment side effects.
The main principle of CT perfusion is obtaining multiple CT images during injection of the iodine contrast bolus. The increased parenchymal density is proportional to the iodine contrast and arterial blood flow. Generally, 35 to 50 milliliter of iodine contrast is injected via the antecubital vein followed by 20 cc of saline. CT acquisition starts five to seven seconds after contrast injection and it continues up to 75 to 90 seconds. The brain coverage CT perfusion depends on the scanner but most of the time the brain at the level of the basal ganglia is evaluated although the new scanners can cover the main part of the brain with a large field of view. Parameters of CBF, CBV, MTT and time to maximum (T-Max) maps are calculated mathematically by non-convolution or deconvolution techniques. Mainly, CBV/CBF is used to for differentiation between core infarction versus peri-infarction ischemia. The area with decreased CBV/CBF is considered to be infarction and the area with increased MTT but relatively preserved CBV or even slightly increased CBV is considered as peri-infarction ischemia (
2). The normal value of the mentioned CTP parameters can be different given different scanners and protocols. The stroke centers are advised to set their own normal values. Generally, MTT about 4 s, CBF about 60 mL/100 g/min and CBV about 4 mL/100 g are considered as normal for gray matter and MTT of 4.8 s, CBF of 25 mL/100 g/min and CBV of 2 mL/100 g are considered normal for white matter. In gray matter, CBF less than 10 - 25 mL/100 g/min and CBV less than 2 mL/100 g are considered as core infarction and relative MTT increase >145% but relatively preserved CBV/CBF is considered as ”ischemic penumbra” ( 3, 4).
Up to 30% of clinically diagnosed acute ischemic strokes are not true stroke but stroke mimics. There are several diseases that can mimic stroke (
5). Stroke mimics can occur in up to 19% of patients initially treated for stroke and in up to 16.7% of patients receiving thrombolytic therapy. Seizures are among the most common stroke differential diagnosis because the ictal and postictal symptoms can mimic stroke symptoms. Focal neurologic deficits can be seen during and after seizure episodes. It can be difficult to distinguish transient, post-ictal neurological deficits following seizure from those because of cerebral ischemia ( 6). In the presented case, loss of consciousness and mild facial asymmetry of the left face (likely Todd’s paralysis) was considered as stroke signs in initial clinical evaluation. It should be noted that loss of consciousness is not a common presentation of focal status epilepticus, but the EEG was localized to the left cerebral hemisphere in this case. During the seizure, the perfusion increases in the involved brain parenchyma but perfusion rapidly reduces, so generally, on CT perfusion there is decreased perfusion in the epileptogenic foci ( 5, 7, 8). In one prior published study, patients with epilepsy (and without infarction) were evaluated by CT perfusion up to 72 hours after the seizure attack. Thirty seven percent of these patients had abnormal perfusion with focal hypo perfusion with prolonged MTT and decreased CBV and CBF being the most common finding followed by hollo-hemispheric hypo perfusion, multi-lobar hypo perfusion and ‘cortical ribbon’ pattern ( 6). In our case, CTP was performed as stroke code few minutes after symptom presentation. CTP showed asymmetry in the right and left cerebral hemisphere with longer MTT and lower CBF and CBV in the right cerebral hemisphere in comparison to the left side. This asymmetry was because of left hollo-hemispheric hyperperfusion which was misinterpreted visually as right hollo-hemispheric hypoperfusion. The concurrent CT angiogram showed asymmetry of cortical branches of the right and left MCA arteries but without evidence of flow limiting stenosis in right-sided arterial circulation.
Figure 5 presents a companion case with similar holo-hemispheric asymmetry in CTP parameters which is identical to the aforementioned case. Visual assessment and the CTP software are not capable of differentiation between these two completely different pathologies. However, by measuring the absolute values of CTP parameters, the differentiation is possible. In the presented patient with seizure, the holo-hemispheric asymmetry is because of left hemispheric hyper perfusion so MTT and time to peak (TTP) of the left hemisphere are less than normal value and the CBV and CBF are more than the normal value. In the companion case, however, the holo-hemispheric asymmetry is because of right hemispheric hypo perfusion. So, MTT, TTP, CBV and CBF parameters of the left hemisphere are within normal limits ( Figure 5).
Prior studies about CTP findings of seizure have been mostly performed post-ictally. Since CTP is now performed in acute setting as a part of stroke code, more CTPs are done during seizure and hyperperfusion of epileptogenic foci is more common than hypoperfusion. In one recent CTP study in “code stroke” patients, about 60% of seizure patients with stroke like symptoms showed hyperperfusion in the involved hemisphere (
5). The radiologist should be aware of increased perfusion in epileptogenic foci and not interpret the contralateral hemisphere as ischemic. Any CTP for “code stroke “should be read by measuring the absolute CBV, CBF and MTT values. Being familiar with the normal perfusion value and paying attention to absolute CBV, CBF and MTT values rather than solo visual assessment can help to avoid this confusion. In addition, the referring physician must provide information to the radiologist about any unusual symptoms that are not classical for ischemia and localize the suspected ischemic hemisphere that would help the radiologist to avoid confusion between normal/hypoperfused hemisphere (ischemia) and normal/hyperperfused hemisphere (seizure).