Meta-Analysis Identifies Characteristics Associated With U …: Neurology Today

Brief article

Based on a meta-analysis of clinical studies, researchers identified transient focal neurological events associated with cerebral amyloid angiopathy and the long-term risk of intracerebral hemorrhage and death.

Neuroimaging results in patients with transient focal neurologic episodes. AB, Patient 16. Multiple cortical and subcortical microbleeds, superficial right fronto-parietal cortical siderosis and right frontal lobar intracerebral hemorrhage (arrowhead) (A). Predominant posterior periventricular white matter hypersignals (arrowhead) and subcortical white matter hypersignals (arrowhead) (B). CE, Patient 10. Focal convex subarachnoid hemorrhage (arrowhead) (C). Fronto-parietal focal cortical superficial siderosis (arrowhead) (D). Forty-five days after image C, acute parietal lobar intracerebral hemorrhage and surrounding superficial cortical siderosis more extensive than in image D (E). CT indicates computed tomography; FLAIR, fluid attenuated inversion recovery; GRE, gradient echo sequences; MRI, magnetic resonance imaging; SWI, susceptibility-weighted imaging.

A new meta-analysis provides much needed information on a rare and often confusing neurological disease – transient focal neurological episodes (TFNE) – resulting from cerebral amyloid angiopathy (CAA).

The article, published online November 15 in JAMA Neurology, defined TFNE as “stereotypical, recurrent and short-lived events (generally 10 to 30 minutes) of focal disturbances, mainly somatosensory or motor”. CAA is a small vessel disease characterized by the deposition of beta-amyloid in cerebral arteries, venules, and capillaries. Intracerebral hemorrhage (ICH) is the most common presentation of CAA, putting patients at high risk for morbidity and death.

CAA-related TFNEs are sometimes misdiagnosed as transient ischemic attacks (TIAs) due to symptomatic similarities, and patients may be given an antithrombotic drug when in fact, antithrombotics can be potentially harmful in this circumstance.

Analysis from Spain shows that patients with ACA-related TFNEs are at high risk of lobar intracerebral hemorrhage (ICH) and death, especially if they are wrongly diagnosed with TIA and prescribed antithrombotics.

TFNEs may be overlooked by clinicians evaluating patients because symptoms may resemble those of TIAs, migraine auras, or focal seizures. “Early diagnosis of ABA is essential to avoid harmful therapies such as antithrombotics in these patients,” said study author Jorge Rodriguez-Pardo, MD, PhD, a stroke neurologist at La Paz University Hospital and Stroke Center in Madrid.

There is still a lot to learn about TFNEs and their relationship to CAA, said Dr Rodriguez-Pardo.

Study design

To learn more about the impact of AFC-related TFNEs, researchers conducted a meta-analysis using data collected from a hospital cohort as well as results obtained from a systematic review of observational reports ( including 42 studies) published in the medical literature from September. 2018 to December 2019. A total of 228 adults (26 of the hospital cohort) with AFN-associated TFNE were included in the analysis, which represents the largest series ever published on the subject, said Dr Rodriguez -Pardo. Patient-level clinical, imaging and prognostic data were required to be included in the analysis. The mean age of the patients was 74 years and 55.6 percent were men.

The main outcomes measured in the meta-analysis were lobar ICH and risk of death during follow-up. The analysis took into consideration the clinical characteristics of TFNE, the neuroimaging characteristics and the use of antithrombotics during follow-up.

Of the 228 AFC-related TFNEs, 108 (43.5%) were motor symptoms and 184 (74.2%) had sensory symptoms. Convex subarachnoid hemorrhage was detected in 193 (77.8%) and superficial cortical siderosis in 156 (62.9%) of the cohort.

During follow-up – at a median of one year for those who had documents – lobar ICH occurred in 76 patients (39.4 percent). Motor symptoms and the use of antithrombotics, in many cases due to misdiagnosis, during follow-up were associated with an increased risk of lobar HIC, the researchers reported.

In bivariate analysis, ICH occurred in 43.8% of patients on antithrombotics and 17.7% of patients without antithrombotics, a 2.5-fold increased risk, Dr Rodriguez-Pardo said.


“To date, the clinical implications of TFNE in patients with CAA have been uncertain. This meta-analysis sheds light on identifiable characteristics associated with a higher risk of adverse outcomes that may be crucial in decision-making, especially regarding antithrombotic therapy. “—DR. JORGE RODRIGUEZ-PARDO

Thirty-one patients (16.5%) died during follow-up, and lobar ICH during follow-up was a risk factor for death. Neuroimaging findings such as superficial cortical siderosis and concomitant small ischemic lesions were also independent risk factors for death, Dr Rodriguez-Pardo said. “The subarachnoid hemorrhage of the convexity was not related to a poorer prognosis as previously indicated. “

The researchers said their findings offer a nuanced view of AFC-related TFNEs. “The TFNEs included in this hospital cohort reveal a semiologically complex entity in which sensory, motor, language and visual symptoms generally coexist,” they wrote. “Pure sensory events accounted for only a third of all episodes and sensory symptoms were absent in almost a third of cases. This finding corroborates the most recent evidence, which suggests that TFNEs exhibit much broader symptoms than previously thought, rendering the classic concept of episodes of positive sensory spread obsolete.

Dr Rodriguez-Pardo said the findings should help neurologists, who are often called upon to sort such cases arriving in the emergency department, to achieve “better management of TFNE patients through better risk assessment. HIC ”.

“To date, the clinical implications of TFNE in patients with CAA have been uncertain,” he said. “This meta-analysis sheds light on identifiable characteristics associated with a higher risk of adverse outcomes that may be crucial in decision making, particularly with respect to antithrombotic therapy.”

Although the study did not directly focus on the issue of imaging, Dr Rodriguez-Pardo said the results suggest “that if there is the slightest suspicion that the patient may have suffered from TFNE related to CAA, an MRI with a blood-sensitive sequence is crucial to avoid a misdiagnosis of TIA.

Investigators acknowledged that the study had limitations, including that there was a lot of heterogeneity in the cohort and that the hospital cases were non-consecutive and retrospective in nature.

Expert commentary

Michelle C. Johansen, MD, PhD, assistant professor of neurology in the Cerebrovascular Division at Johns Hopkins University School of Medicine, said the new study provides important insight because “outside of vascular neurologists there are many people may not be able to recognize transient foci. neurological episodes as being caused by AAC.

She said she often sees misdiagnosed cases, even in some patients already known to have AAC; in particular, with the misdiagnosis of AFN-related TFNEs as seizures.


“The public health message is that AAC and these transient events are linked. Taking the time, even in the midst of a busy emergency department, to take a good history and talk to the patient and their family can help make the correct diagnosis. “—DR. MICHELLE C. JOHANSEN

“The public health message is that CAA and these transient events are linked,” Dr. Johansen said. She said that as a clinician she was particularly interested in the study which found that many of “these transient events have a motor component.”

“Taking the time, even in the midst of a busy emergency department, to take a good history and talk to the patient and their family can help make the correct diagnosis,” she said.

Eric E. Smith, MD, PhD, professor of neurology at the University of Calgary in Canada and the Kathy Taylor Chair in Vascular Dementia, said it can be difficult to recognize AFC-related TFNEs, in part because they are much less common than TIA and often AAC itself has not been diagnosed before.

He said the symptoms of TFNE, which can come and go over a short period of time, can be distressing for patients and also confusing because “you have symptoms and then you get better.”

“About 1% of patients thought they had had a TIA [actually] have had CAA-related TFNE, ”said Dr Smith, who co-authored a review article on CAA-related TFNE that was first published online in May in Neurology.

He said doing “an MRI with sensitivity-weighted sequences can identify signs of chronic bleeding, such as superficial cortical siderosis, which may alert the clinician to the possibility that the transient symptoms were caused by the ‘AAC’.

While there is no disease-modifying treatment for CAA, Dr Smith said it is important to diagnose CAA “because we can probably reduce their risk of bleeding by avoiding unnecessary antithrombotics. “.

“What you want to avoid is giving medicine like aspirin for what is thought to be a transient ischemic attack because this condition [CAA] could increase the risk of future bleeding, ”he said.

Steven M. Greenberg, MD, PhD, FAAN, professor of neurology at Harvard Medical School, said bleeding most commonly associated with CAA-related TFNEs tends to show up on MRI scans as “pretty patterns. distinctive on the surface of the brain ”. with telltale blood products “following the folds and valleys of the brain.” We will often have what looks like a river path.

Dr Greenberg, who heads the Hemorrhagic Stroke Research Program at Massachusetts General Hospital, said, “Treating CAA-related TFNEs is as much what you don’t do as it is what you do. The clearest and most convenient thing you can do is not give antithrombotic drugs. Keeping blood pressure under control can also help prevent future bleeding. “


Drs. Rodriguez-Pardo and Johansen had no disclosure. Dr Smith received consulting fees from Bayer, Biogen Cyclerion and Javelin.