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We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects.Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform.Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation.Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022;92:1090-1101.

α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) encephalitis is rare but treatable. We reviewed the clinical and autoantibody profiles of 52 AMPAR-IgG-positive patients (median age 48 years [range 12-81]; 38 female) identified at the Mayo Clinic neuroimmunology laboratory. Main presentation was encephalitis; symptoms other than encephalitis associated with co-existing antibodies (p = 0.004). A tumor was found in 33/44; mostly thymoma. Most patients had partial (14/29) or complete (11/29) immunotherapy response. Thirty-one patients had at least one co-existing antibody that predicted thymoma in paraneoplastic patients (p = 0.008). In conclusion, in AMPAR encephalitis co-existing antibodies predict clinical presentation other than encephalitis and thymoma.

The Careggi Collateral Score (CCS) (qualitative–quantitative evaluation) was developed from a single-centre cohort as an angiographic score to describe both the extension and effectiveness of the pial collateral circulation in stroke patients with occlusion of the anterior circulation. We aimed to examine the association between CCS (quantitative evaluation) and 3-month modified Rankin Scale (mRS) score in a large multi-center cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1284 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery (ACA)-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Using CCS of 4 as reference, CCS grades were associated in the direction of unfavourable outcome on 3-month mRS shift (0 to 6); significant difference was found between CCS of 0 and CCS of 1 and between CCS of 3 and CCS of 4. CCS ≥ 3 was the optimal cut-off for predicting 3-month excellent outcome, while CCS ≥ 1 was the optimal cut-off for predicting 3-month survival. CCS of 0 and CCS

The diagnosis of peripheral neuropathies can be challenging with consequent difficulties in patients' management. The aim of this study was to explore the current diagnostic role of sural nerve biopsy and to compare pathological findings with serum neurofilament light chain levels (NfL) as biomarkers of axonal damage. We collected demographic, clinical, and paraclinical data of patients referred over 1 year to the Neurology Unit, University of Verona, Italy, to perform nerve biopsy for diagnostic purposes, and we analyzed NfL levels in available paired sera using a high sensitive technique (Quanterix, Simoa). Eighty-two patients were identified (37.8% females, median age 65.5 years). Neuropathy onset was frequently insidious (68.3%) with a slowly progressive course (76.8%). Lower limbs were usually involved (81.7%), with a predominance of sensory over motor symptoms (74.4% vs 42.7%). The most common neuropathological findings were a demyelinating pattern (76.8%), clusters of regenerations (58.5%), and unmyelinated fibers involvement on ultrastructural evaluation (52.4%). A definite pathological diagnosis was achieved in 29 cases, and in 20.7% of patients, the referral clinical diagnosis was modified. Coexistent hematological conditions and hepatitis were diagnostic confounding factors (p = 0.012 and 0.034, respectively). In the analyzed paired sera (n = 37), an inverse despite not significant relationship between NfL values and fiber density was observed (Spearman's rho - 0.312, p = 0.056). In addition, we noted increased serum NfL values of patients with active axonal degeneration. Nerve biopsy remains a useful diagnostic investigation to achieve a correct diagnosis and guide patients' management in selected cases of peripheral neuropathy. Serum NfL is an accessible and potential valuable marker of axonal damage in these conditions.

Neurological autoimmunity is increasingly recognized as a complication of immune checkpoint inhibitor (ICI) cancer immunotherapy. ICIs act by enhancing endogenous anti-tumor immune responses and can also lead to autoimmunity affecting all organs. ICI-related neurological autoimmunity is rare, most often manifests with neuromuscular involvement and more rarely affects the central nervous system. Neurological complications often often present in the first three months of ICI treatment but can also appear after ICI discontinuation. These can occur in patients with tumors not traditionally associated with paraneoplastic neurological autoimmunity, such as melanoma and renal-cell carcinoma and should be suspected when a new neurological symptoms present while on ICI and cannot be explained by disease progression or as a consequence of metabolic dysfunction. Treatment consists of ICI discontinuation or withdrawal depending on the severity with or without immunosuppression. Generally, improvement is observed depending on the patient's baseline characteristics and neurological presentation.

Symptomatic lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent the acute manifestations of type 1 cerebral small vessel disease (cSVD). Recently, two studies showed that the risk factor profile of dICH differs from that associated with LS in subjects with biologically plausible cSVD; however, the prognostic predictors after acute manifestations are currently lacking. We aimed to develop a nomogram for individualized prediction of the mortality probability in a cohort of patients with a first-ever acute manifestation of biologically plausible cSVD.We conducted a retrospective analysis of data collected from consecutive patients with acute symptomatic non-embolic LS or primary dICH. The outcome measure was 3-month mortality. Based on multivariate logistic model, the nomogram was generated.Of the 288 patients who entered into the study for biologically plausible cSVD, 131 (45%) experienced a LS and 157 (55%) a dICH. After multivariate logistic regression, 5 variables remained predictors of mortality to compose the nomogram: dICH (OR:11.36; p=0.001), severe presentation (OR:8.08; p0.001), age (OR:1.08; p=0.001), glucose (OR:1.23; p=0.003) and creatinine (OR:1.01; p=0.024) at admission were predictors of mortality. The discriminative performance of nomogram assessed by using the area under the receiver operating characteristic curve (AUC-ROC) was 0.898. The model was internally validated by using bootstrap (1000 samples) with AUC-ROC of 0.895 and cross-validation (deleted-d method repeated 1000 times) with AUC-ROC of 0.895.We developed the first nomogram for prediction of the mortality probability in a cohort of patients with a first-ever acute manifestation of biologically plausible cSVD.

Intracerebral hemorrhage (ICH) growth is an important independent predictor of clinical deterioration and outcome. Little is known about the association between etiology of ICH and occurrence of hematoma expansion (HE). The aim of the present study was to assess whether ICH etiologic subtype may influence the risk of significant HE.We conducted an analysis on retrospectively collected data of 424 consecutive patients with ICH, who were admitted to the Verona General Hospital, from March 2011 to December 2014. Using the SMASH-U (Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined) classification, we identified the ICH etiologic subtypes. Outcome measure was significant HE (an absolute increase in ICH volume12.5 mL or50%) within 48 h.Significant HE occurred in 11/57 (19.3%) Amyloid, 7/14 (50%) Structural, 31/57 (54.4%) Medication, 25/44 (56.8%) in Systemic, 62/139 (44.6%) Hypertensive, and 21/68 (30.9%) Undetermined ICH. Baseline ICH volume (OR 1.011 per mL, 95% CI 1.006-1.017, p0.001) and onset-to-baseline CT time (OR 0.919 per hour, 95% CI 0.852-0.990, p=0.027) were predictors of significant HE. Compared with Amyloid ICH, ORs for significant HE were higher in patients with Structural ICH (OR 1.430, 95% CI 1.060-1.948, p=0.023), Medication ICH (OR 4.344, 95% CI 1.382-13.653, p=0.012), Systemic ICH (OR 1.796, 95% CI 1.070-3.015, p=0.027), and Hypertensive ICH (OR 3.081, 95% CI 1.426-6.655, p=0.004).Our study shows that Structural, Medication, Systemic, and Hypertensive ICH were the etiologic subtypes associated with a higher risk of significant HE, compared with Amyloid ICH patients.