Health-related quality of life in patients with brain arteriovenous malformation

Brain arteriovenous malformations (AVM) are rare vascular anomalies in which the cerebral arteries and veins are connected without the normal intervening capillary bed. Most often, in roughly half of the cases, the event leading to diagnosis is intracranial hemorrhage. The second most common symptom is a focal epileptic seizure, leading to diagnosis in one-third of the cases. AVM incidence in the general population is approximately 1/100,000 person-years. The average age for AVM diagnosis is slightly over 30 years, meaning that the disease often affects working-age people. It is also a significant cause of intracranial hemorrhage in children and young adults. The AVM hemorrhage is lethal in, on average, 5–25% of patients. In this thesis we have studied patients in the Helsinki AVM database using the 15D health-related quality of life (HRQoL) instrument and questionnaire data about lifestyle. Our database consists of 805 AVM patients treated in the Helsinki University Hospital Department of Neurosurgery between 1942 and 2014. Of them, 325 patients answered the mailed questionnaire sent in 2016 and comprise the study cohort of this thesis. Our research revealed that after a mean 17.6 years (SD ±12.0 yr) of follow-up the HRQoL of treated AVM patients in general was, when considering the difficulty of the disease, only modestly decreased. Also, most of the patients had been able to return to work. In the multivariate model, the decreased HRQoL of AVM patients was explained by older age, sex (being female), difficult refractory epilepsy, difficult location or structure of the AVM, and more than one hemorrhagic episode. Our results support active AVM treatment in those cases which the procedure can be done safely and the treatment-related risks do not exceed the estimated cumulative rupture risk. Another novel finding from our study cohort was that the prevalence of smokers was significantly higher in AVM patients when compared to a matched general population. The high prevalence, especially during the diagnosis, inspires more vigorous investigation of the role of cigarette smoking in the currently unknown etiology of AVMs. With our final article, we participated in the on-going discussion in the scientific community about the statistical handling of the commonly used functional outcome instrument, the modified Rankin Scale. We showed, using our AVM patient cohort, that the popular dichotomous approach in outcome assessment could significantly bias research results.Aivojen valtimolaskimoepämuodostumat (AVM) ovat harvinaisia verisuoniepämuodostumia, joissa aivovaltimot ja -laskimot ovat yhdistyneet ilman normaalia hiussuoniverkostoa. Diagnoosiin useimmiten, noin puolessa tapauksista, johtava syy on aivoverenvuoto. Toiseksi yleisimmin diagnoosiin johtaa epileptinen kohtaus, noin kolmanneksella potilaista. AVM:ien ilmaantuvuus väestössä on keskimäärin 1/100 000 henkilövuotta. Keskimäärin AVM diagnosoidaan hieman yli 30-vuotiailla. Sairaus koskettaakin usein työikäisiä ja se on yksi merkittävistä lasten ja nuorten aikuisten aivoverenvuodon aiheuttajista. Potilaista, joilla AVM puhkeaa, aivoverenvuoto johtaa kuolemaan noin 5-25%:ssa tapauksista. Tässä väitöskirjatyössä on tutkittu Helsinki AVM -aineiston potilaita käyttäen 15Delämänlaatumittaria ja kyselykirjeitse saatua dataa liittyen potilaiden elintapoihin. Tietokantaamme on kerätty vuosina 1942-2014 Helsingin yliopistollisen sairaalan Neurokirurgian klinikassa hoidetut AVM-potilaat (n=805). Heistä 325 vastasi vuonna 2016 lähetettyyn elämänlaatukyselykirjeeseen ja muodostaa tämän väitöskirjan päätutkimuskohortin. Tutkimuksemme paljasti, että keskimäärin 17.6 vuoden (SD=±12.0v) seuranta-ajan jälkeen hoidettujen AVM-potilaiden elämänlaatu oli, ottaen huomioon taudin vaikeusasteen, ainoastaan maltillisesti madaltunut. Lisäksi, suurin osa potilaista oli kyennyt palaamaan työelämään. Monimuuttujamallissa heikentynyttä elämänlaatua selittäviä tekijöitä AVM-potilaiden välillä olivat vanhempi ikä, naissukupuoli, vaikea jäännösepilepsia, AVM:n vaikea anatominen sijainti tai rakenne, ja useampi kuin yksi aivoverenvuoto. Tutkimustuloksemme kannustavat AVM:n aktiiviseen hoitoon niissä tapauksissa, joissa toimenpide voidaan suorittaa turvallisesti, eivätkä toimenpiteen riskit ylitä arvioitua elinaikana kertyvää vuotoriskiä. Toinen uusi löydös tutkimuskohortistamme oli, että tupakoivien AVM-potilaiden esiintyvyys on huomattavasti korkeampi kuin tupakoijien osuus suomalaisessa verrokkiväestössä. Erityisesti tupakoijien suuri määrä AVM:n diagnoosivaiheessa kannustaa tutkimaan tupakoinnin osuutta AVM:ien nykyhetkellä tuntemattomassa etiologiassa. Lopulta, otimme tutkimuksellamme kantaa tiedeyhteisössä käytävään keskusteluun yleisesti käytetyn modified Rankin Scale -luokituksen tilastollisesta käsittelystä. Osoitimme käyttämällä AVM-potilailtamme saatua 15D-elämänlaatudataa, että tutkimuksissa usein käytetty kahtiajakoon pohjautuva luokittelu saattaa merkittävästi vääristää tutkimustuloksia

Arteriovenous Malformations of the Posterior Fossa : Focus on Surgically Treated Patients Presenting with Hemorrhage

BACKGROUND: Arteriovenous malformations (AVMs) of the posterior fossa are demanding lesions that often present with rupture. Studies including outcome analyses in surgically operated patients with ruptured infratentorial AVMs are scarce. Certain anatomic and demographic features have shown associations with postoperative outcomes. METHODS: Eighty-six patients with infratentorial AVM were collected from our AVM database. Fifty-four patients were admitted from 1990 onward, and their demographic, lesion, and treatment characteristics were analyzed. The cohort was further refined to 38 consecutive patients with surgically treated ruptured infratentorial AVM admitted to our center between 1990 and 2014, and statistical analyses of factors influencing outcomes were conducted. RESULTS: Twenty-seven patients (69%) had a favorable outcome at early follow-up and 24 (67%) had a favorable outcome at final follow-up. Factors associated with poor outcome in early recovery on univariate analyses were deep venous drainage of the lesion (odds ratio (OR 5.3; P = 0.037) and high Hunt & Hess score (P = 0.003). In the multivariate model, independent predictors for poor outcome were deep venous drainage (OR, 14.5; P = 0.010) and older age at admission (OR, 1.06; P = 0.028). The sole independent predictor for poor outcome at last follow-up was deep venous drainage (OR, 5.00; P = 0.046). The total follow-up time was 370 person-years. CONCLUSIONS: AVMs of the posterior fossa usually present with rupture and thus require prompt clinical treatment. The majority of surgically treated patients recover favorably. Our data show that venous drainage patterns have the greatest influence on the patient's postoperative condition. Other influencing factors include the severity of hemorrhage and patient age at admission.Peer reviewe

Comparing health-related quality of life in modified Rankin Scale grades : 15D results from 323 patients with brain arteriovenous malformation and population controls

Background We wanted to understand how patients with different modified Rankin Scale (mRS) grades differ regarding their health-related quality of life (HRQoL) and how this affects the interpretation and dichotomization of the grade. Methods In 2016, all adult patients in our brain arteriovenous malformation (AVM) database (n = 432) were asked to fill in mailed letters including a questionnaire about self-sufficiency and lifestyle and the 15D HRQoL questionnaire. The follow-up mRS was defined in 2016 using the electronic patient registry and the questionnaire data. The 15D profiles of each mRS grade were compared to those of the general population and to each other, using ANCOVA with age and sex standardization. Results Patients in mRS 0 (mean 15D score = 0.954 +/- 0.060) had significantly better HRQoL than the general population (mean = 0.927 +/- 0.028), p < 0.0001, whereas patients in mRS 1-4 had worse HRQoL than the general population, p < 0.0001. Patients in mRS 1 (mean = 0.844 +/- 0.100) and mRS 2 (mean = 0.838 +/- 0.107) had a similar HRQoL. In the recently published AVM research, the most commonly used cut points for mRS dichotomization were between mRS 1 and 2 and between mRS 2 and 3. Conclusions Using 15D, we were able to find significant differences in the HRQoL between mRS 0 and mRS 1 AVM patients, against the recent findings on stroke patients using EQ-5D in their analyses. Although the dichotomization cut point is commonly set between mRS 1 and 2, patients in these grades had a similar HRQoL and a decreased ability to continue their premorbid lifestyle, in contrast to patients in mRS 0.Peer reviewe

Long-term health-related quality of life in 262 patients with brain arteriovenous malformation

Tausta: Aivojen valtimo-laskimoepämuodostumaa (AVM) sairastavien potilaiden terveyteen liittyvästä elämänlaadusta ei ole aikaisempaa tutkimustietoa. Menetelmät: Vuonna 2016 elossa oleville AVM-rekisterimme potilaille (n=432) lähetettiin kyselykirjeet, jotka sisälsivät 15D-elämänlaatukyselykaavakkeen. Kyselyyn vastanneista tutkimukseemme valittiin potilaat, joiden AVM oli kokonaan onnistuttu poistamaan (n=262). Potilaiden vastauksia verrattiin suomalaiseen normaaliväestöön ikä- ja sukupuolivakioidusti. Lisäanalyyseja tehtiin tutkimuksen AVM-potilaiden välillä verraten ryhmiä modified Rankin Scale -arvon, jäännösepilepsian asteen, vuototapahtumien lukumäärän, AVM:n sijainnin ja Spetzler-Ponce-luokituksen (SPC) mukaan. Tobit-regressiomallia käytettiin selittämään 15D-arvon varianssia monimuuttujamallissa. Tulokset: AVM-potilaiden terveyteen liittyvä elämänlaatu oli heikentynyt verrattuna normaaliväestöön pitkäaikaisseurannassa (p < 0.0001). AVM:n syvä sijainti aivoissa, useat vuototapahtumat ja jäännösepilepsia assosioituivat heikentyneeseen elämänlaatuun. SPC A- ja SPC B -potilailla oli samankaltainen elämänlaatu seurannassa, kun taas SPC C -potilaiden elämänlaatu oli heikentynyt näihin verrattuna. Monimuuttujamallissa selittäviä muuttujia heikentyneelle elämänlaadulle olivat korkea ikä, naissukupuoli, useat vuototapahtumat, jäännösepilepsia ja SPC C -luokan AVM. Yhteenveto: Huolella valitut SPC B -potilaat voivat saavuttaa yhtä suotuisan elämänlaadun pitkäaikaisseurannassa kuin SPC A -potilaat, kunhan toimenpiteessä onnistutaan poistamaan AVM kokonaisuudessaan. Vuototapahtumia tulisi pyrkiä ehkäisemään tehokkaalla hoidolla, sillä ne heikentävät pitkäaikaista elämänlaatua entisestään. AVM-potilaiden leikkauksenjälkeisen hoidon tulisi keskittyä nykyistä enemmän masennuksen, ahdistuksen ja jäännösepilepsian ehkäisyyn ja hoitoon.Objective: To discover the health-related quality of life (HRQOL) of patients with treated arteriovenous malformation (AVM), we used the self-applicable HRQOL instrument, the 15D, and analyzed the scores in both in the whole study population and specified cohorts. Methods: The 15D questionnaires were mailed to adult patients with AVM alive in 2016 (n = 432) in our database. Patients with completely eradicated AVM (n = 262) were included in a subsequent analysis. The results were compared with those of the general population standardized for age and sex. Subgroup analyses were conducted for epilepsy, number of bleeding episodes, location of the lesion, modified Rankin Scale score, and Spetzler-Ponce classification (SPC) using independent-samples t test or analysis of covariance. Tobit regression was used to explain the variance in the 15D score. Results: Patients had impaired HRQOL compared to the reference population (p < 0.0001). Deep location, multiple bleeding episodes, and refractory epilepsy were associated with impaired HRQOL. Patients in SPC A and B had similar posttreatment 15D scores, whereas those in class C had an impaired HRQOL. Significant explanatory variables in the regression model were age, sex, number of bleeding episodes, refractory epilepsy, and SPC. Conclusions: With careful patient selection, patients in SPC B can reach as favorable HRQOL as those in SPC A provided the operation is successful. Multiple bleeding episodes should be prevented with effective treatment aiming at complete AVM obliteration. The postoperative treatment of patients with AVM should focus on preventing depressive symptoms, anxiety, and epileptic seizures. We encourage other research groups to use HRQOL instruments to fully understand the consequences of neurologic and neurosurgical diseases on patients’ HRQOL

Coexistence of intracranial dysraphic cyst and aneurysm : A qualitative systematic review and multiple management portraits

Background: The coexistence of intracranial aneurysms and dysraphic cysts is a rare manifestation. The response triggered by the cyst and its proinflammatory content could play a role in the rupture or growth of a neighboring aneurysm. Methods: We performed a systematic review according to the PRISMA guidelines searching PubMed, Medline, Google Scholar and Embase. Additionally, we report a case of one patient with both a dermoid cyst and an ipsilateral anterior cerebral artery aneurysm, illustrating a progressive formation of the vascular lesion during the follow-up of the cyst. Results: Out of 103 papers fulfilling the inclusion criteria for the systematic review, 79 articles were selected for eligibility. Finally, a total of 9 cases, including our own case, were considered for the review. We found that all aneurysms were in the anterior circulation and all cysts were supratentorial. The aneurysms or parent vessels were in proximity or in contact with the dysraphic lesion, presenting a strong adherence to its capsule. The 3 dermoids presented with cysts rupture and showed simultaneous or delayed subarachnoid aneurysmal hemorrhage. Two epidermoid cysts were diagnosed after aneurysm rupture, while the others due to focal mass effect, as in the case of the neurenteric cyst. Conclusions: Coexistence of intracranial aneurysm and disraphic cyst is a rare finding with multiple possible presentations. In managing patients harboring disraphic cyst, the presence of the aneurysm should be ruled out during the standard workup. A coexistence of these pathologies could affect their natural histories, and this could justify a more active management protocol.Peer reviewe

Hemangioblastoma and arteriovenous malformation in the same patient : a not random association or two isolated entities? Systematic review starting from a unique case

Background: The association between intracranial hemangioblastomas and arteriovenous malformations has been documented in very few cases in literature since 1965 and might present in three modalities: "intermixed, adjacent and separated (spatially and temporally)”. Often, the pattern of presentation is “intermixed”. According to our systematic review, we propose an adjustment of the previous classification, specifically for these entities. We describe the first case of a truly “spatially separated” association between these two lesions. Methods: Our study encompassed all adult patients diagnosed with both intracranial hemangioblastoma and AVM who were evaluated in the last 20-year period, from 2003 to 2023 at Helsinki University Hospital. Cases of this coexistence were retrospectively identified and collected from clinical records. For the systematic review, studies reporting the coexistence of hemangioblastoma and AVM in adult patients (>18 years old) were selected. Given the rarity of this pattern, case reports were also included. Results: The combined analysis of our systematic review and institutional retrospective study revealed a total of only seven identified cases. We applied the classification of neoplasms and AVM by Yano, modifying and adapting it into our screened patient series. We systematically reclassified “adjacent” and genuinely “spatially separated” patterns based on the vascular axis supplying both lesions. Conclusions: Hemangioblastomas and AVMs rarely coexist in the same patient. Our study reports the first instance of a truly “spatially separated” sporadic association between these vascular lesions. The rarity of such coexistence underscores the need for a nuanced and systematic classification to guide the management of these infrequent cases.Peer reviewe

Coexistence of intracranial dysraphic cyst and aneurysm: A qualitative systematic review and multiple management portraits

Background: The coexistence of intracranial aneurysms and dysraphic cysts is a rare manifestation. The response triggered by the cyst and its proinflammatory content could play a role in the rupture or growth of a neighboring aneurysm. Methods: We performed a systematic review according to the PRISMA guidelines searching PubMed, Medline, Google Scholar and Embase. Additionally, we report a case of one patient with both a dermoid cyst and an ipsilateral anterior cerebral artery aneurysm, illustrating a progressive formation of the vascular lesion during the follow-up of the cyst. Results: Out of 103 papers fulfilling the inclusion criteria for the systematic review, 79 articles were selected for eligibility. Finally, a total of 9 cases, including our own case, were considered for the review. We found that all aneurysms were in the anterior circulation and all cysts were supratentorial. The aneurysms or parent vessels were in proximity or in contact with the dysraphic lesion, presenting a strong adherence to its capsule. The 3 dermoids presented with cysts rupture and showed simultaneous or delayed subarachnoid aneurysmal hemorrhage. Two epidermoid cysts were diagnosed after aneurysm rupture, while the others due to focal mass effect, as in the case of the neurenteric cyst. Conclusions: Coexistence of intracranial aneurysm and disraphic cyst is a rare finding with multiple possible presentations. In managing patients harboring disraphic cyst, the presence of the aneurysm should be ruled out during the standard workup. A coexistence of these pathologies could affect their natural histories, and this could justify a more active management protocol

Changes in treatment of intracranial aneurysms during the last decade in a large European neurovascular center

Objective: Treatment modality for ruptured and unruptured intracranial aneurysms has shifted during the last two decades from microsurgical treatment towards endovascular treatment. We present how this transition happened in a large European neurovascular center. Methods: We conducted a retrospective observational study consecutive patients treated for an unruptured or ruptured intracranial aneurysm at Helsinki University Hospital during 2012–2022. We used Poisson regression analysis to report age-adjusted treatment trends by aneurysm location and rupture status. Results: A total of 2491 patients with intracranial aneurysms were treated (44% ruptured, 56% unruptured): 1421 (57%) surgically and 1070 (43%) endovascularly. A general trend towards fewer treated aneurysms was noted. The proportion of patients treated surgically decreased from 90% in 2012 to 20% in 2022. The age-adjusted decrease of surgical versus endovascular treatment was 6.9%/year for all aneurysms, 6.8% for ruptured aneurysms, and 6.8% for unruptured aneurysms. The decrease of surgical treatment was most evident in unruptured vertebrobasilar aneurysms (10.8%/year), unruptured communicating artery aneurysms (10.1%/year), ruptured communicating artery aneurysms (10.0%/year), and ruptured internal carotid aneurysms (9.0%/year). There was no change in treatment modality for middle cerebral artery aneurysms, of which 85% were still surgically treated in 2022. A trend towards an increasing size for treated ruptured aneurysms was found (p = 0.033). Conclusion: A significant shift of the treatment modality from surgical to endovascular treatment occurred for all aneurysm locations except for middle cerebral artery aneurysms. Whether this shift has affected long-term safety and patient outcomes should be assessed in the future.Peer reviewe