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Cannabis use is very frequent in CH patients, but its efficacy for the treatment of the attacks is limited. Less than one third of self-reported users mention a relief of their attacks following inhalation. Cannabis should not be recommended for CH unless controlled trials with synthetic selective cannabinoids show a more convincing therapeutic benefit.

Background and purpose. -To compare outcomes of minor stroke patients with intracranial vessel occlusions (IVO) underwent mechanical thrombectomy (MT) versus those treated with intravenous thrombolysis alone (IVT). Methods. -We retrospectively reviewed two large prospective stroke databases from two European centers searching for patients admitted with minor stroke (i.e. NIHSS Score ≤ 5), baseline mRS = 0 and occlusion of the M1-M2 segment of the middle cerebral artery (MCA). Groups receiving (A) IVT alone and (B) MT+/-IVT were compared. Primary outcome measures were MT safety, successful recanalization rate (mTICI 2b-3) and NIHSS shift (discharge NIHSS minus admission NIHSS); secondary outcomes included discharge rates and excellent outcome (mRS 0-1) at 3 months. Univariate and multivariate analyses were performed.Results. -Thirty-two patients were enrolled in Group B (19 MT alone; 13 MT + IVT) and 24 in Group A. Successful recanalization (mTICI 2b-3) was obtained in 100% of cases in Group B vs 38% in Group A. Symptomatic hemorrhagic transformation rate did not differ between the two groups. Multivariate analysis reported MT as the only predictor of early (< 12 h) favorable NIHSS shift and lower NIHSS at discharge. Moreover, discharge at home and excellent outcome at 3-month follow-up were statistically associated with MT. Conclusions. -MT in patients with minor strokes and intracranial vessel occlusion (IVO) is safe and can determine a rapid improvement of NIHSS Score. MT seems also associated with a higher rate of patients discharged at home after hospitalization and better clinical outcome at 3-month follow-up. Larger randomized trials are warranted to confirm these results.

Limbic encephalitis (LE) with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leukocyte antigen (HLA), and CSF proteomic profiles. Patients with anti-AK5 LE were mostly men (20/26, 76.9%) of median age 66 years old (range 48-94). Predominant symptom was severe episodic amnesia in all patients, frequently associated with depression (17/25, 68.0%). Weight loss, asthenia, and anorexia were also highly characteristic, being present in 11/25 (44.0%) patients. Although epilepsy was always lacking at disease onset, seizures developed later in a subset of patients (4/25, 16.0%). All patients presented CSF abnormalities, such as pleocytosis (18/25, 72.0%), oligoclonal bands (18/25, 72.0%), and increased Tau (11/14, 78.6%). Temporal lobe hyper-intensities were almost always present at disease onset (23/26, 88.5%), evolving nearly invariably toward a severe atrophy in subsequent MRIs (17/19, 89.5%). This finding was in line with a poor response to immunotherapy, with only 5/25 (20.0%) patients responding. IgG1 was the predominant subclass, being the most frequently detected and the one with highest titres in nine CSF-serum paired samples. Temporal biopsy from one of our new cases showed massive lymphocytic infiltrates dominated by both CD4+ and CT8+ T-cells, intense granzyme B expression, and abundant macrophages/microglia. HLA analysis in 11 patients showed a striking association with HLA-B*08:01 (7/11, 63.6%; OR = 13.4, 95% CI [3.8-47.4]), C*07:01 (8/11, 72.7%; OR = 11.0, 95% CI [2.9-42.5]), DRB1*03:01 (8/11, 72.7%; OR = 14.4, 95% CI [3.7-55.7]), DQB1*02:01 (8/11, 72.7%; OR = 13.5, 95% CI [3.5-52.0]), and DQA1*05:01 (8/11, 72.7%; OR = 14.4, 95% CI [3.7-55.7]) alleles, which formed the extended haplotype B8-C7-DR3-DQ2 in 6/11 (54.5%) patients (OR = 16.5, 95% CI [4.8-57.1]). Finally, we compared the CSF proteomic profile of five anti-AK5 patients with that of 40 controls and 10 cases with other more common non-paraneoplastic LE (five with antibodies against leucine-rich glioma inactivated 1 and five against contactin-associated protein-like 2), as well as 10 cases with paraneoplastic neurological syndromes (five with antibodies against Yo and five against Ma2). These comparisons revealed, respectively, 31 and seven significantly up-regulated proteins in anti-AK5 LE, mapping to apoptosis pathways and innate/adaptive immune responses. These findings suggest that the clinical manifestations of anti-AK5 LE result from a distinct T-cell mediated pathogenesis, with major cytotoxicity-induced apoptosis leading to a prompt and aggressive neuronal loss, likely explaining the poor prognosis and response to immunotherapy.

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