Teenage stroke: a brief insight with a description of two cases


 Introduction:Acute ischemic stroke (AIS) in teenagers occurs infrequently and is a real emergency with serious consequences for patients and their families. Both thrombectomy and thrombolysis are well tolerated but are still debated. Nowadays there are not sufficient data concerning the outcome of these treatments and only few studies and case reports proved their efficacy and safety.Case presentation:Herein we present two reports of AIS in adolescents, for which different therapeutic approaches were performed, achieving a successful outcome in both cases without short or long-term complications.Conclusions:The early recognition of teenage stroke is not always easy, due to the variability of causes and symptoms, but a good outcome can be achieved with reperfusive treatments performed as quickly as possible.


Introduction
Acute ischemic stroke (AIS) in children and adolescents is very rare but represents one of the most important cause of disability and death at a young age 1 . The annual incidence for AIS in adolescence is ranging from 0.54 to 2.4 per 100,000 with a signi cant male predominance 2,3 . Teenage stroke (TS) has a signi cant impact on quality of life, work capacity and family costs representing a serious social disease, because of its association with high follow-up costs and long-term rehabilitative treatment 2 . The etiology of TS presents several differences from adults, varying with age, race and sex. Black and Asian adolescents have an increased risk of AIS because of a stronger predisposition for sickle cell anemia and iron de ciency, respectively 4 . In younger patients, the clinical picture is different from adult stroke, due to the total absence of the conventional risk factors, such as hypertension or diabetes. We described two cases of TS in patients aged 16 and 17, respectively, admitted to comprehensive stroke center (CSC) of Messina, Italy, between 2018 and 2020. A correct and prompt diagnosis allowed achieving good outcomes in terms of prognosis and residual neurological de cits.

Case 1
A 17-year old girl was admitted to CSC for sudden loss of consciousness followed by global aphasia and severe right-sided hemiplegia (National Institute of Health Stroke Scale, NIHSS: 13). She had a history of migraine with aura, polycystic ovary syndrome (for which she was assuming estrogen-progestogen therapy from one year), and seizure-like episodes, occurred about three times before stroke event and characterized by severe pulsating headache, sweating, trembling and short-lasting loss of consciousness.
Cerebral computed tomography (CT) was normal. Brain magnetic resonance imaging (MRI) showed hyperintensities in left frontal lobe, with "spaghetti sign" on uid attenuated inversion recovery (FLAIR) sequences. On MR angiography (MRA), M2 segment of left middle cerebral artery (MCA) and A2 and A3 segments of anterior cerebral artery (ACA) could not be visualized. MRI perfusion-diffusion mismatch predicted favorable outcomes to reperfusion (Fig. 1). After parental consent was obtained (underage patient), she underwent bridging therapy, combining intravenous thrombolysis with tissue-type plasminogen activator (IVT) at standard dose (0.9 mg/kg) and mechanical thrombectomy (MT) with optimal results. Ultrasonography (US) of the carotid and vertebral arteries was normal. Transcranial color doppler ultrasound (TCCD) detected the transit of microbubbles through a patent foramen ovale (PFO).
The transesophageal echocardiography (TEE) con rmed the presence of a large-sized PFO (tunnel length > 10 mm). The patient reported no neurological sequelae, with NIHSS 0 at discharge. Two weeks after discharge, the patient has reported three recurrent seizures characterized by short periods of absence, treated with lacosamide (100 mg daily).

Case 2
A 16-year-old boy was admitted to CSC for acute onset of dysarthria and right hemiparesis occurred during a swimming competition (NIHSS 11). Brain CT and MRI did not show abnormalities. Parental consensus was obtained and the patient was treated with IVT outside the therapeutic indications. About three hours after the end of IVT, neurological examination showed severe aphasia and right hemiplegia (NIHSS 15), but new CT brain was unchanged. Subsequently the patient showed progressive clinical improvement. The next day, MRI revealed nucleo-capsular hyperintensity on diffusion-weighted imaging (DWI) and FLAIR sequences, and MRA showed a suspected partially occlusive thrombus on the left MCA ( Fig. 2). Nevertheless, repeated CTA and MRA checks did not showed the thrombus previously described, with patency of circle of Willis. All diagnostic tests performed during hospitalization such as carotid US, TCCD, transthoracic echocardiography (TTE), TEE and bilateral leg US were normal. Screening for rare causes of stroke, coagulopathies or trombophilic and autoimmune diseases were unremarkable. We started therapy with acetylsalicylic acid 100 mg/day and intensive rehabilitation. After ten days, the patient was discharged as cryptogenic stroke with moderate recovery of speech and motility (NIHSS 4).
At twenty-four months follow-up, he reported slight weakness to the right leg (NIHSS 1).

Discussion
Infections, cardiac diseases, traumatic dissections, vasculopathies and hereditary coagulopathies are the most relevant risk factors in TS, although it often remains cryptogenic. Due to the rarity of the disease and the variability of clinical manifestations, diagnosis is often delayed. Younger patients frequently present seizures as rst manifestations of AIS. Alteration of consciousness may also be seen 1 . The gold standard for diagnosis is DWI-MRI, characterized by low radiation risk and able to detect AIS within a short time. The optimal treatment approach in these patients remains unclear. Nowadays, the number of cases in which thrombolysis and endovascular therapy are performed has increased, even in very young patients, supporting the e cacy and safety of reperfusion treatments 3 . The atypical episodes preceding AIS in case n.1, could be interpreted as seizures. Moreover she developed a post-stroke epilepsy. Both migraine and PFO has been involved occasionally in AIS, and their correlation especially with the PFO is probabilistic 3 . Migraine with aura is associated with an approximately two-fold increased risk of AIS in adults, while migraine aura state should be studied as a possible risk factor for stroke in younger patients 5 . Furthermore the use of estrogenic oral contraceptives is known to be associated with an increased risk of stroke in adult women affected by migraine with aura 5 , but there are not su cient data to demonstrate similar association in adolescents. To determine stroke etiology is even more di cult in case n. 2, because no cause of AIS was identi ed during the diagnostic evaluations. Even after the ndings of the suspected subocclusive thrombus in left MCA, showed one day after the AIS at MRA, MT was not performed due to the progressive regression of symptoms. Serial follow-up radiological controls have shown the possible artifact of the ndings.

Conclusion
The diagnosis of TS is challenging and options for the acute treatment are limited. It is well known that stroke in this very young patients is a real emergency and must be treated as quickly as possible. We presented two different cases of TS undergone different therapeutic approaches, aiming to contribute to data literature about the e cacy of reperfusion treatments with IVT and MT.
Both treatments are not recommend as a standard therapeutic option, due to the bleeding risk, but their use is increasing due to their e cacy and safety. Funding: this research did not receive any speci c grant from funding agencies in the public, commercial, or not-for-pro t sectors.
Magnetic resonance imaging (MRI). Fluid attenuated inversion recovery (FLAIR) showing hyperintensity in left frontal lobe (A); FLAIR revealing «spaghetti sign» on fronto-temporal lobes and interhemispheric ssure (B); the same leptomeningeal collaterals were lightened on pseudocontinuous arterial spin labeling (pc-ASL) (C); on MR angiography (MRA), time of ight (TOF) sequences revealed M2 segment of left middle cerebral artery (MCA) and A2-A3 segments of anterior cerebral artery (ACA) could not be visualized (D); MRA control revealed the patency of the very same segments of left MCA and ACA with ow retrieval (E).

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