VASCULITI PRIMITIVE DEL SISTEMA NERVOSO CENTRALE: APPROCCIO DIAGNOSTICO

Le vasculiti primitive del sistema nervoso centrale (PACNS) sono malattie rare, potenzialmente fatali, ad eziologia sconosciuta. L'esordio clinico si caratterizza principalmente per la comparsa di cefalea e/o encefalopatia. La diagnosi di certezza può essere formulata solo con la biopsia cerebrale; in assenza di conferma bioptica, i dati clinici, laboratoristici e di imaging devono essere considerati nell’insieme per rafforzare l’ipotesi diagnostica. Gli esami ematochimici sono generalmente nella norma. Lo studio del liquor evidenzia anomalie non specifiche nella maggior parte dei casi: le alterazioni più comuni sono un aumento delle proteine e/o della conta dei leucociti. La RM convenzionale rivela alterazioni in tutti i pazienti; più frequentemente si evidenziano infarti corticali-subcorticali multipli e bilaterali, a volte in associazione a lesioni emorragiche intraparenchimali e/o subaranoidee. L’angio-RM può essere utile nelle prime fasi d’indagine; questa tecnica è tuttavia meno sensibile dell’angiografia, soprattutto nello studio del circolo posteriore e dei vasi di piccolo calibro. L’angiografia cerebrale riesce ad evidenziare segni di infiammazione dei vasi fino a 250-500µm di diametro; i reperti più comuni sono stenosi multisegmentarie, aneurismi, trombosi multiple dei vasi. La biopsia cerebrale rimane il gold standard nella diagnosi di PACNS. L’aspetto istopatologico è quello di una vasculite transmurale e segmentaria; per tale motivo una biopsia negativa non esclude completamente una PACNS. Data l’assenza di biomarkers di malattia e la necessità di ricorrere ad esami invasivi quali l’angiografia e/o la biopsia cerebrali, questa tesi si è proposta di ricercare nuovi approcci diagnostici nello studio delle PACNS

Validation Study Of The International Classification Criteria For The Cryoglobulinemic Vasculitis

Background/Purpose: preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been developed in 2011 by an European cooperative study, with an adequate methodology in a large number of real cases and controls (1). The aim of this study is to validate these classification criteria for CV. Methods: Centres from Europe, United States, Japan and Egypt, were involved. A dedicated chart included: l) a validated questionnaire for CV (1); 2) the pattern of organ involvement (4 items: constitutional, articular, vascular and neurologic involvement); 3) laboratory tests (3 items: rheumatoid factor, complement C4 and serum monoclonal component), according to the preliminary criteria (1). New patients with CV (Group A) and controls (Group B), i.e., subjects with cryoglobulins but lacking CV based on the golden standard clinical judgment, were studied. A sample size of at least 140 patients for each group was estimated in order to obtain a sensitivity and a specificity of at least 90.5%, based on the previous results (1). Sensitivity and specificity were calculated by comparing Group A versus Group B. Finally, not for classification purposes, but to disclose whether the Criteria may be also clinically helpful in patients lacking serum cryoglobulins, but where CV is suspected (1), Group A was also compared with Group C, including patients with diseases mimicking CV, but without serum cryoglobulins. Results: Six hundred forty-three patients were enrolled in 22 Centres (from Italy, Spain, France, Greece, Slovenia, Japan and Egypt). MajorA comprised 268 patients with CV, Group B 182 controls with serum cryoglobulins without CV, and Group C 193 controls without serum cryoglobulins. Notably, 20 patients showed type I cryoglobulinemia, 13 in Group A, and 7 in Group B. Group C included 108/193 (55.9%) systemic vasculitides, 100/108 (92.6%) were small vessel vasculitides. The classification criteria [positivity of at least 2/3 items among questionnaire (2/3 positive questions), clinical item (3/4 clinical manifestations), laboratory (2/3 tests)] showed 89.9% (95% CI 86.1–93.6) of sensitivity and 93.5% (95% CI 89.7–97.2) of specificity, replicating previous results (1). Sensitivity of 91.7% and specificity of 100% were observed in the subgroup of type I cryoglobulinemia. By the comparison of Group A vs. Group C, the Criteria showed a specificity 92.6% (88.8–96.5) and a sensitivity of 77.8% (72.6–83.0) when the laboratory item was positive (questionnairelaboratory item; or clinical laboratory item). Conclusion: the International Classification Criteria for the CV have been validated in a new real cohort. High specificity and sensitivity were confirmed. Notably, in patients where CV is suspected on clinical grounds, but where cryoglobulins are negative by initial testing, or not yet available (patients who cannot be classified as CV, as positive serum cryoglobulinemia is a conditio sine qua non for classification) (1), the Criteria appear relevant to strengthen the suspicion for CV, and to optimize the follow-up