Authors: Kenza Berrada, Ibtissam El Ouali, Salma El Aouadi, Meryem Fikri, Mohamed Jiddane, Firdaous Touarsa
Categories: Case Report, Stroke, Ischemia, MRI, Negative-diffusion
Source: Radiology Case Reports
Authors: Kenza Berrada, Ibtissam El Ouali, Salma El Aouadi, Meryem Fikri, Mohamed Jiddane, Firdaous Touarsa
Ischemic stroke is a medical emergency that’s typically identified early using MRI, particularly with diffusion-weighted imaging (DWI). However, some rare but important cases present without the usual DWI findings, posing a diagnostic challenge. We describe the case of a 75-year-old woman with a history of hypertension and diabetes who woke up with weakness on her left side and facial asymmetry. Her initial brain MRI showed no abnormalities on DWI, but ASL imaging revealed reduced perfusion in the right hemisphere, and MR angiography identified an occlusion of the right internal carotid artery. Follow-up CT and MRI scans later confirmed a large right-sided infarct. This case underscores the value of multimodal imaging and the importance of repeating MRI when clinical suspicion for stroke remains high, even if the initial scan appears normal
Stroke stands as a prominent cause of disability and mortality worldwide. The occurrence of an acute ischemic stroke arises when an artery that supplies the brain becomes obstructed, resulting in the death of brain tissue and the manifestation of focal neurological deficits. Recently, diffusion-weighted imaging (DWI) has proven to be an outstanding tool for the early detection of acute strokes. Early DWI not only aids in diagnosis but has also emerged as an independent predictor for favorable outcomes in patients with ischemic stroke. However, despite its high accuracy, there is a reported non-negligible rate of false negatives. The failure to diagnose acute strokes due to DWI-negativity presents a significant risk, potentially leading to delayed or missed treatment plans and an increased likelihood of recurrent strokes. We report a case of We report a case of 75-year-old female patient who presented to the emergency department with a stroke upon awakening, initial MRI of brain didn’t show any restriction on diffusion-weighted imaging sequence.
We report the case of a 75-year-old female patient with a 5-year history of diabetes and hypertension, who presented to the emergency department with left hemiplegia and facial paralysis upon waking. Initially, the patient underwent an emergency brain MRI that did not reveal any lesions on the diffusion-weighted imaging sequence (Fig. 1A). Given the occurrence of a stroke upon awakening, a rapid MRI protocol was implemented, including an arterial spin labeling (ASL) sequence, which demonstrated diffuse right hemispheric hypoperfusion (Fig. 1B). The contrast-enhanced supra-aortic trunk MR angiography revealed the absence of opacification of the internal carotid artery from its postbulbar portion to the extra-cranial level, with a flame-shaped stoppage (Fig. 2).Fig. 1Images showing absence of restrictive diffusion on B1000 (A), with low perfusion on the right hemisphere on ASL sequence (B).Fig Fig. 2Supra-aortic trunk angiography showing the absence of opacification of the internal carotid artery from its postbulbar portion to the extra-cranial level, with a flame-shaped stoppage.Fig
On the same day, immediately after the MRI, a cerebral CT scan was performed, showing no particular findings (Fig. 3). As there was no recovery of clinical deficit and facial paralysis, the diagnosis of ischemic stroke with normal diffusion was considered. Twenty-four hours after the initial MRI, a second CT scan revealed a hypodense area in the corona radiata and at the junction of the medial third and lateral two-thirds of the frontal lobe, corresponding to the anterior right deep and superficial junctional stroke (Fig. 4). A follow-up MRI after 25 hours from the first MRI showed signal restriction throughout the hemisphere on the diffusion-weighted imaging sequence (Fig. 5).Fig. 3Initial axial sections (A and B) of nonenhanced CT with no abnormalities.Fig Fig. 4Twenty-four hours after the initial MRI, a second CT scan revealed a hypodense area in the corona radiata (A) and at the junction of the medial third and lateral two-thirds of the frontal lobe (B), corresponding to the anterior right deep and superficial junctional stroke.Fig Fig. 5Immediately after the positivity of the second CT, Diffusion sequences showed a restriction on the whole right hemisphere.Fig
Stroke stands as a leading cause of disability and death globally. It is characterized by a sudden injury to the central nervous system, often stemming from an acute ischemia. Recognized as a potentially treatable medical emergency, ischemic stroke comes with a critical time window for intervention. In Morocco, the estimated prevalence rate of stroke across all age groups is 292 per 100,000 [1].
Strokes are defined by a sudden cessation of the central nervous system's function following a sudden cerebral assault. This assault has commonly an arterial ischemic origin. It is an urgent medical emergency, with functional and vital prognoses depending on the timeliness of diagnosis and intervention, often referred to as “time is brain.”
On a physiological level, ischemia results from a decrease or interruption in cerebral blood circulation. This leads to a reduction in glucose and oxygen supply, resulting in the accumulation of metabolites in nervous tissue’s cells. Cerebral blood flow (CBF) is estimated at approximately 50 mL per 100 g of brain tissue per minute. The cessation of cerebral perfusion leads to a loss of neuronal electrical activity within seconds. A reduction in cerebral blood flow less than 20 mL/100 g/min induces reversible disturbances lasting several hours, while a drop below 10 mL/100 g/min results in irreversible brain damage within minutes. A reduction of more than 50% in cerebral blood flow leads to a decrease in protein synthesis, triggering anaerobic glycolysis, lactate production, and the release of neurotransmitters such as glutamate into the extracellular space. This causes an impairment of the Na+/K+ pump, an increase in intracellular potassium concentration, intracellular entry of K+ leading to intracellular edema, activation of proteolytic enzymes, and the death of glial and neuronal cells. The concept of the “penumbra” is associated with the fact that the sudden obstruction of an artery does not uniformly reduce cerebral blood flow. Thus, within the ischemic focus, there is a central zone with cerebral blood flow less than 10 mL/100 g/min, marked by irreversible intracellular changes, and known as the core of infarctus, and a peripheral zone, known as the penumbra, with cerebral blood flow between 10 and 20 mL/100 g/min. In this penumbral zone, electrical activity disappears, but without irreversible cellular changes [2].
Recently, the use of brain’s MRI, in the assessment of acute ischemic stroke (AIS) has seen a significant increase .Ever since Moseley et al. [3] described a 30% to 50% decrease in the water diffusion constant in cases of acute cerebral feline ischemia, diffusion-weighted MR imaging has proven to be a valuable tool for the early diagnosis of stroke in humans. It has demonstrated significantly higher sensitivity (88%-100%) and specificity (95%-100%) [5] compared to conventional T2-weighted MR imaging or CT in detecting early changes associated with hyperacute stroke (within 6 hours) [4] . However, recent meta-analyses reveal a noteworthy finding, approximately 6.8% of AIS cases are reported as DWI-negative, indicating that despite its overall effectiveness, DWI may not identify abnormalities a small significant portion of AIS cases [6]. DWI lesions occasionally appear on follow-up MRI in patients initially clinically suspected of having a stroke but were negative for DWI. Only few clinical reports and systemic study regarding the delayed onset of DWI lesions are reported [7,8]. In a specific study, the delayed DWI time for lesion detection ranged widely from 8 hours to 144 hours [9]. Another report documented an exceptionally prolonged delayed DWI time, lasting 336 hours (2 weeks), though such extreme delays in DWI time appear to be rare [10].
The prevalence rate of false-negative DWI is reported to range between 1.5% and 25.6% [9,11]. Sylaja et al. observed that out of 401 patients, 25.6% exhibited false-negative DWI results [11]. The final clinical diagnoses for these cases included transient ischemic attack (61.2%), stroke (25.2%), and nonischemic causes (13.6%). In a study by Oppenheim et al, the rate of false-negative DWI was found to be 5.8% (8 out of 139) among patients with ischemic stroke [7].
Three potential mechanisms may explain the lack of diffusion changes in the acute phase in patients with eventual symptoms of infarction.
Initially, it is plausible that cerebral blood flow (CBF) existed at an intermediate level, situated below the threshold for neuronal dysfunction (symptom onset) but above that associated with reduced diffusion. Hössman [12] has recently conducted a comprehensive review of the literature on blood flow thresholds in ischemia, primarily in animal models. Generally, the suppression of EEG activity, corresponding to the onset of deficits, occurs when perfusion is in the range of 15 to 20 mL/100 g per minute (30% to 40% of the normal CBF of 50 mL/100 g per minute) [13,14]. In contrast, membrane pump failure [15] does not occur until below 10 to 15 mL/100 g per minute [16]. Cerebral blood flow reductions lead to hypoperfusion, sufficient to generate symptoms but not severe enough to yield diffusion positivity. Consequently, hypoperfusion without restricted diffusion may be observable. In a recent study, 44% of patients with ischemic stroke, initially presenting a perfusion deficit on the MRI scan, exhibited at least 1 new DWI lesion in the subsequent week [17,18].
Another mechanism contributing to DWI-negative ischemic strokes may be attributed to recanalization, rendering the DWI image appear normal [19,20]. However, this does not prevent eventual delayed infarction [21]. Spontaneous recanalization can be observed in up to 25% of cases with ischemic stroke [22,23]. Still, when it occurs very early, it might result in an “aborted stroke.” The concomitant pseudo-normalization of the DWI signal could obscure the appearance in the initial imaging, becoming more evident during follow-up. The phenomenon of spontaneous recanalization is associated with both clinical improvements and electrophysiologic recovery [17,24]. This scenario is akin to a transient ischemic attack (TIA) when it occurs spontaneously, not as a consequence of recanalization treatments such as thrombectomy.
Third, it is possible that a second ischemic event may have caused the eventual infarction. This seems unlikely, however, except in those patients in whom significant neurologic deterioration occurred after the initial imaging [17].
A recent report has suggested the proportion of false-negative DWI relative to lesion location and MR latency [7]. Within the initial 24 hours, the rate of false-negative DWI studies was significantly higher when strokes occurred in the posterior circulation (31%) compared to the anterior circulation (2%). Brain stem lesions, in particular, were at a heightened risk of being overlooked by DWI [7]. In general, patients with small vertebrobasilar stroke lesions, imaged shortly after symptom onset, were most prone to negative DWI findings. Several factors may contribute to this phenomenon. Firstly, the lesions could be too small for the resolution of the DWI echo-planar sequence. This hypothesis gains support from the fact that FLAIR images, boasting higher spatial resolution, revealed signal abnormalities in half the lesions not visible on DWI. Secondly, the signal-to-noise ratio might be inadequate in the initial hours after onset. Lastly, magnetic susceptibility artifacts occurring in echo-planar imaging could distort the brain stem, potentially blurring image analysis. The use of DWI with turbo spin-echo sequences could address these technical limitations by providing high-resolution images with fewer susceptibility artifacts, especially in the posterior fossa [7].
In a study conducted by Kitae et al. [25] involving 827 patients initially presenting with DWI-negative stroke, 156 cases (22.5%) exhibited positive conversion of DWI lesions. The group that underwent positive conversion demonstrated a significantly elevated risk of recurrent stroke, all-cause mortality, and composite vascular outcomes compared to the nonconversion group. Various clinical factors, signs, and symptoms were associated with DWI conversion, including atrial fibrillation (AF), smoking, prestroke dependency, early neurological deterioration, objective hemiparesis, longer symptom duration, high cholesterol, NIHSS score, and high systolic blood pressure at presentation. To aid in identifying patients with a higher likelihood of DWI conversion among initially DWI-negative cases, Kitae et al. developed the DWI-CONVERSION score using readily available clinical features and patients' signs and symptoms in the emergency room (Table 1, Table 2) [25].Table 1Diffusion DWI-Conversion score (0-39 points) to predict delayed DWI lesions.Table Clinical factorPointsTotal cholesterol level (mg/dL) >2404 ≤2400Blood pressure (mm Hg) Systolic BP ≥180 or diastolic BP ≥1102 180> systolic BP ≥160 or 110> diastolic BP ≥1001 Systolic BP<160 and diastolic BP<100, simultaneously0Symptom duration (min) ≥604 10-592 0-9 or unclear0Atrial fibrillation Yes6 No0Habitual smoking Current or ex-smoker3 Never smoker0Objective motor power MRC grade of arm <5 and MRC grade of leg <5, simultaneously2 Other0Aphasia Yes (any type of aphasia)3 No0Dysarthria and subjective hemiparesis Dysarthria and subjective hemiparesis, simultaneously4 Other0Veering tendency and time from first symptom onset to initial MRI (h) Veering tendency and <96, simultaneously2 Other0Sensory Paresthesia and hypesthesia, simultaneously3 Other0Prestroke mRS* ≥26 12 00⁎mRS: modified ranking scaleTable 2Observed incidence of DWI-positive conversion on follow-up MRI.Table DWI-CONVERSION scoreDWI-negative in follow-up (total cohort)Positive conversion in follow-up (total cohort)0-4224155-921370≥105171
<< DWI-CONVERSION score>> predict the likelihood that a patient who has a negative DWI scan at first will develop positive DWI findings later, indicating an actual ischemic stroke.
This score is based on clinical features (Table 1) observed at the time of presentation. Each factor contributes points, and the total score helps estimate the risk of DWI lesion “conversion” (delayed visibility of stroke).
Tables 2 explain actual observed rates of DWI lesion appearance on follow-up MRI depending on the DWI-CONVERSION score.
The results of this study may contribute to the formulation of clinical guidelines pertaining to admission, vigilant monitoring in a stroke unit, and follow-up DWI scans during in-hospital care.
While diffusion-weighted imaging (DWI) has proven to be an excellent tool for the early diagnosis of acute ischemic stroke, it is important to note that false-negative results are not uncommon. This report emphasizes that the absence of abnormalities on DWI does not exclude the possibility of acute ischemic stroke. Consequently, in cases where a patient exhibits persistent neurological deficits despite a negative DWI, it is advisable to conduct follow-up DWI examinations for a more comprehensive assessment and accurate diagnosis.
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The corresponding author is the guarantor of submission.