Central nervous system immune-related disorders after SARS-CoV-2 vaccination: a multicenter study.

Background: COVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination. Methods: Multicenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) de novo CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis. Results: Nineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2. Conclusion: CNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.

The Present and Future of Optic Pathway Glioma Therapy.

Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients.

Clinical applicability of arterial spin labeling magnetic resonance imaging in patients with possible idiopathic normal pressure hydrocephalus: A prospective preliminary study.

PURPOSE: idiopathic Normal Pressure Hydrocephalus (iNPH) patients have a global reduction of cerebral blood flow (CBF) and Arterial Spin Label (ASL) MRI allows a global evaluation of CBF without the injection of contrast agents. This work aims to assess the qualitative evaluation agreement of ASL CBF colored maps between different neuroradiologists and by correlating these data to the Tap Test. METHODS: Thirty - seven patients with the diagnosis of possible iNPH were consecutively submitted to a diagnostic MRI on a 1.5 Tesla Magnet before and after the lumbar infusion test and the Tap Test. Twenty - seven patients improved after the Tap Test and were addressed to surgery while 10 patients did not improve. All the MRI examinations included a 3D-Pulsed ASL sequence. Two different neuroradiologists independently reviewed all ASL images. They were asked to give a score (0 not improved; 1 improved) to global perfusion image quality by comparing ASL images obtained after the Tap Test to those obtained before. Comparison between inter- and intra-reader qualitative scores were performed with Cohen's kappa. RESULTS: Inter-reader agreement between the two neuroradiologists showed that qualitative scores were attributed similarly by two readers (k = 0.83). This technique has a good PPV (90.5 %; CI 95 %, 72.7-97.1 %), NPV (50 %; CI 95 %, 34.1-65.6 %), SN (70.37 %; CI 95 %, 49.8-86.2 %) SP (80 %; CI 95 %, 44.4-97.5 %) and accuracy (73 %; CI 95 %, 55.9-86.2 %) when considered in the setting of possible iNPH patients. CONCLUSION: ASL-MRI seems to be a promising non-invasive technique in the preoperative selection of patients affected by possible iNPH.

MDS-UDPRS-III in the diagnosis of idiopathic Normal Pressure Hydrocephalus and identification of candidates for Ventriculo-Peritoneal Shunting surgery. Results from a retrospective large cohort of patients.

OBJECTIVES: To evaluate the entity of extrapyramidal signs, characterize them and evaluate the dynamics of change by the mean of MDS-UPDRS-III in iNPH patients after the TT to determine if this tool may help the diagnosis of iNPH and the identification of candidates for Ventriculo-Peritoneal Shunting. MATERIALS AND METHODS: We retrospectively collected data from 120 patients with the initial diagnosis of possible iNPH; they underwent neurological examination by the means of MDS-UPDRS-III and other scales before and after Tap Test (TT). They were then classified as defined iNPH (57), probable iNPH (35), and NOT-iNPH (28) based on the clinical response after the Tap Test and VPS. RESULTS: After the Tap Test, defined and probable iNPH groups improved by 3.35 (2.57-4.12, p < 0.001) and 3.43 (2.43-4.4, p < 0.001) points on MDS-UPDRS-III respectively; NOT-iNPH did not improve significantly on MDS-UPDRS-III and on any other variable studies. Defined iNPH also shifted significantly from asymmetric prevalence of symptoms to a more symmetric form (from 70% before to 57% after). CONCLUSION: extrapyramidal signs improved significantly after the Tap Test in definite and probable iNPH patients. MDS-UPDRS-III may be a useful complementary tool in the diagnosis of iNPH and identification of candidates for Ventriculo-Peritoneal Shunting.

New-onset Myasthenia Gravis after SARS-CoV-2 infection: case report and literature review.

We report the case of a 19-year-old female patient who developed Myasthenia Gravis 13 days after SARS-CoV-2 infection with positive RT-PCR testing. Her symptoms initially involved the oculo-bulbar district, but they gradually worsened in 3 months converting into a generalized form of Myasthenia Gravis complicated with a myasthenic crisis. A high level of anti-acetylcholine receptor antibodies was found in the serum, while anti-MuSK antibodies were negative; Repetitive Nerve Stimulation and Single-fiber Electromyography were suggestive of Myasthenia Gravis. Intravenous immunoglobulin courses and specific therapy were able to improve her symptoms, but thymic resection was needed to control the disease. This is a report of new-onset Myasthenia Gravis correlated to COVID-19 in which thymic resection was described and the histologic analysis of the thymus was performed showing thymic hyperplasia despite negative thoracic Magnetic Resonance Imaging. SARS-CoV-2 infection releases inflammatory cytokines that could dysregulate the immune system and lead to Myasthenia Gravis in susceptible subjects.

Risk Factors for Intraoperative Seizures in Glioma Surgery: Electrocorticography Matters.

PURPOSE: Few and contradictory data are available regarding intraoperative seizures during surgery for low-grade gliomas. Aim of this study was to evaluate possible risk factors for the occurrence of IOS. METHODS: The authors performed a retrospective analysis of 155 patients affected by low-grade gliomas and tumor-related epilepsy, who underwent surgery in our Department, between 2007 and 2018. A statistical analysis was performed by means of univariate and multivariate regression to evaluate any possible correlation between seizure occurrence and several demographic, clinical, neurophysiological, and histopathological features. RESULTS: Intraoperative seizure occurred in 39 patients (25.16%) with a total of 62 seizure events recorded. Focal seizures were the prevalent seizure type: among them, 39 seizures did not show motor signs, being those with only electrographic and/or with cognitive features the most represented subtypes. Twenty-six seizures occurring during surgery were not spontaneous: direct cortical stimulation with Penfield paradigm was the most prevalent evoking factor. The univariate analysis showed that the following prognostic factors were statistically associated with the occurrence of intraoperative seizure: the awake technique ( P = 0.01) and the interictal epileptiform discharges detected on the baseline electrocorticography (ECoG) ( P < 0.001). After controlling for confounding factors with multivariate analysis, the awake surgery and the epileptic ECoG pattern kept statistical significance. CONCLUSIONS: The awake surgery procedure and the epileptic ECoG pattern are risk factors for intraoperative seizure. ECoG is mandatory to detect electrographic seizures or seizures without motor signs.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.

In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer.

Pre- and Post-surgical Poor Seizure Control as Hallmark of Malignant Progression in Patients With Glioma?

Background: Regarding brain tumor-related epilepsy (BTRE), there is an increasing number of evidence about a relationship between epileptogenesis and oncogenesis. A recent study suggests a role of post-surgery seizure outcome on the survival of patients with low-grade glioma (LGG), underlying the need for a targeted and aggressive epilepsy treatment. Objective: This study aims at investigating the possible correlation between pre- and post-surgical seizure control and tumor progression in patients who underwent surgery for LGG. Methods: We performed a retrospective analysis of patients affected by LGGs and BTRE, in a single high-volume neurosurgical center. Seizure control was assessed before surgery and at 3 years of follow-up. Patients with histological progression in high-grade glioma (HGG) have been evaluated. Clinical features, pre-surgical electroencephalograms (EEGs), and electrocorticography (ECoG) have been analyzed. Results: Among 154 subjects, we collected 32 patients who presented a tumor progression in HGG during the follow-up period. The majority had poor seizure control both pre- and post-surgery, never being in Engel class Ia throughout the whole history of their disease. Almost all patients with poor seizure control had pathological ECoG recording. Clinical features of seizures did not correlate with seizure outcome. On the univariate analysis, the age, the post-operative Engel class, and the extent of resection (EOR) were the prognostic factors significantly associated with oncological outcome; nevertheless, on multivariate analysis, Engel class significance was not confirmed, and the only predicting factor were age and EOR. Conclusions: Although not confirmed on multivariate analysis, post-surgical seizure control could be a relevant factor to consider during follow-up of BRTE, in particular, when gross total resection is not achieved. Pathological findings on the ECoG may suggest a "hidden" propensity to malignant progression, strictly related to the persistent neuronal hyper-excitability. Further studies with longer follow-up period are needed to confirm our observations.

The persistence of seizures after tumor resection negatively affects survival in low-grade glioma patients: a clinical retrospective study.

INTRODUCTION: Seizures are the most common clinical manifestation of low-grade glioma (LGG). Many papers hypothesized an influence of epilepsy on glioma progression. To our knowledge, no clinical study demonstrated a direct relationship between persistence of epileptic seizures after surgery and overall survival (OS) in LGG patients. The present study aims at investigating the correlation between post-operative seizure outcome and survival in tumor-related epilepsy (TRE) patients. METHODS: We performed a retrospective analysis of adult patients affected by TRE who underwent surgery for resection of LGG in a single high-volume neurosurgical center. Seizure outcome was assessed 1 year after surgery and categorized according to Engel classification. Clinical, molecular and radiological features were evaluated in univariate and multivariate analyses to investigate the correlation with OS. RESULTS: A total of 146 patients met the inclusion criteria. Histopathological diagnosis was Diffuse Astrocytoma isocitrate dehydrogenase (IDH) wild type in 16 patients (11%), Diffuse astrocytoma IDH mutated in 89 patients (61%) and oligodendroglioma IDH mutated, 1p 19q codeleted in 41 patients (28%). 1 year after surgery, 103 (70.6%) patients were in Engel class 1. Median duration of follow-up period was 69.5 months. Median OS was 79.3 (72.2-86.4) months in the whole population, while it was 86.8 (78.4-95.2), 63.9 (45.7-82), 63.7 (45.2-82.2) and 47.5 (18.3-76.6) months for patients in Engel class 1, 2, 3 and 4, respectively. In a univariate analysis, Engel class evaluated 1 year after surgery significantly influenced OS (p < 0.01). Multivariate analysis showed that OS was independently associated with extent of resection (p = 0.02), molecular class (p < 0.01) and Engel class (p = 0.04). CONCLUSIONS: Seizure control 1 year after surgery significantly predicted survival of patients affected by LGG-related epilepsy in a large monocentric retrospective series. Future studies are needed to confirm these results and to assess if an epilepsy-surgical therapeutic approach may improve OS.

Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians.

The most recent International League Against Epilepsy (ILAE) classification has included "immune etiology" along with other well-known causes of epilepsy. This was possible thanks to the progress in detection of pathogenic neural antibodies (Abs) in a subset of patients, and resulted in an increased interest in identifying potentially treatable causes of otherwise refractory seizures. Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). To consider these aspects, conceptual definitions for two entities were provided: acute symptomatic seizures secondary to AE, and autoimmune-associated epilepsy, which reflect the different pathophysiology and prognoses. Through this manuscript, we provide an up-to-date review on the current state of knowledge concerning diagnosis and management of patients with Ab-mediated encephalitis and associated epilepsy. Special emphasis is placed on clinical aspects, such as brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) specificities, electroencephalographic (EEG) findings, cancer screening and suggestions for a rational therapeutic approach.

Acute disseminated encephalomyelitis after SARS-CoV-2 vaccination.

Several central and peripheral nervous system complications associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection have been recently described. An effective mass vaccination program is necessary to effectively reduce infection spread and, consequently, limit long-term sequelae, including those affecting the nervous system. Nevertheless, as more patients gain access to coronavirus disease 2019 (COVID-19) vaccines, it is important to report potential adverse events. Herein, we report a patient with previous history of post-infectious rhombencephalitis who developed an acute disseminated encephalomyelitis (ADEM) two weeks after being vaccinated for COVID-19.

Recanalisation theraphy for acute ischemic stroke in cancer patients.

To date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42-20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.

Hyposmia and Dysgeusia in COVID-19: Indication to Swab Test and Clue of CNS Involvement.

OBJECTIVE: To evaluate the prevalence of hyposmia and dysgeusia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their temporal relationship with the onset of other symptoms. METHODS: We performed a retrospective analysis of patients admitted during the month of March 2020 to the nonintensive COVID unit of Udine University Hospital on the basis of a positive swab test and/or of clinical-radiologic signs of SARS-CoV-2 infection. Patients were interviewed with a standardized questionnaire. Clinical and laboratory data were collected. Data were analyzed with descriptive statistics, and results expressed as point estimates and 95% confidence intervals (CIs). RESULTS: Of 141 patients admitted, 93 were interviewed. Hyposmia and dysgeusia were present in 58 cases (62.4%). In 22.4% of them, olfactory and gustatory impairment clearly preceded systemic symptoms. The presence of active smoking was very limited in both groups: 8.6% in hyposmic vs 2.9% in normosmic patients (odds ratio 3.2; 95% CI 0.3-28.6). Moreover, total leukocytes and neutrophils count were respectively 23% (effect estimate 1.23; 95% CI 1.06-1.42) and 29% (effect estimate 1.29; 95% CI 1.07-1.54) lower in the hyposmic cohort. No difference was found for other inflammatory biomarkers. CONCLUSIONS: Hyposmia and dysgeusia are common in SARS-CoV-2 infection and can precede systemic symptoms. They should be actively searched and prompt close monitoring and isolation until infection is confirmed or disproven. The lower number of total leukocytes and neutrophils in hyposmic patients might indicate an early-phase virus-induced cytopenia.

Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review.

OBJECTIVE: To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs). METHODS: Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, 59%; p < 0.001). Anti-programmed cell death protein 1/programmed cell death ligand 1 was more frequent in myasthenic syndromes (50/58, 86%; p = 0.005) and less common in meningitis (2/13, 15%; p < 0.001) and cranial neuropathies (13/31, 42%; p = 0.005). Anti-cytotoxic T-lymphocyte antigen-4 ICIs were more frequent in meningitis (8/13, 62%; p < 0.001) and less common in encephalitis (2/56, 4%; p = 0.009) and myositis (12/136, 9%; p = 0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; p = 0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; p = 0.003) and less common in encephalitis (19/56, 34%; p = 0.001). The highest mortality rate was reached in myasthenic syndromes (28%). CONCLUSION: Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.

Lower lymphocyte counts and older age are associated with reduced multiple sclerosis disease activity during dimethyl fumarate treatment.

BACKGROUND: delayed-release dimethyl fumarate (DMF) is a disease modifying therapy for relapsing-remitting multiple sclerosis (MS) with antioxidant and anti-inflammatory properties. The drug causes lymphocyte count reduction, which can lead to lymphopenia development during treatment. This is an important safety issue, due to infectious risk, mainly progressive multifocal leukoencephalopathy (PML). If the lymphocyte count influences the response to treatment is still a matter of debate, as there are contrasting contrasting data in the literature. Considering this, we aimed to identify DMF induced lymphopenia risk factors and to evaluate lymphopenia impact on MS disease activity in a real world setting. METHODS: a retrospective study on 135 MS patients receiving DMF with a mean treatment duration of 32.3±15.9 months was performed. Baseline and follow-up demographic, clinical, magnetic resonance imaging (MRI) and laboratory data were collected. RESULTS: 44 patients (32.6%) developed lymphopenia, with 11 (8.1%) grade 1, 23 (17.0%) grade 2 and 10 (7.4 %) grade 3. Older age and lower basal absolute lymphocyte count were found to be associated with lymphopenia development on a binary regression model (p<0.001 and p=0.009). When compared with non lymphopenic+lymphopenia grade 1 patients, those experiencing lymphopenia grade 2+3 had longer disease activity free survival (p<0.001), fewer clinical relapses (p=0.005) and lower MRI disease activity (p≤0.001). On Cox regression model, older age and lymphopenia grade 2+3 were found to be protective factors against disease activity (HR=0.966; 95% C.I.=0.942-0.992; p=0.009 for age; HR=0.137; 95% C.I.=0.043-0.439; p=0.001 for lymphopenia grade 2+3) and MRI disease activity (HR=0.968; 95% C.I.=0.941-0.997; p=0.030 for age; HR=0.142; 95% C.I.=0.034-0.591; p=0.007 for lymphopenia grade 2+3). Only lymphopenia grade 2+3 was found to be a predictor of clinical relapses (HR=0.970; 95% C.I.=0.936-1.005; p=0.095 for age; HR=0.115; 95% C.I.=0.016-0.854; p=0.034 for lymphopenia grade 2+3), with a protective effect. CONCLUSION: older age and lower basal lymphocyte count were found to be associated with lymphopenia development. Lymphopenia grade 2+3 and older age could be protective against clinical and radiologic disease activity during DMF treatment.

What's behind drawing for an artist with left temporal lobe epilepsy? A multimodal neurophysiological study.

There are few studies in literature reporting drawing as a strong trigger of praxis-induced focal seizures. The aim of the present case report was describing a case of focal epilepsy with praxis induced EEG activation, due to a cavernoma, in the left middle anterior temporal lobe by using a multimodal approach. We combined video-EEG, showing that drawing increased a sustained monomorphic delta activity localized on left anterior temporal region (F7-T1a), diffusing to the vertex (Fz) and the fronto-polar electrodes (F3), with DTI data, showing that the left uncinate fasciculus, connecting the temporal pole to the orbitofrontal cortex, significantly differed from controls. fMRI confirmed that drawing increased activation in these areas. The congruence between findings supports the role of the left uncinated fasciculus linking the temporal lobe to the orbitofrontal cortex in the present focal epilepsy mainly facilitated by drawing.

Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder.

OBJECTIVE: To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD). METHODS: We fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests. The contribution of biallelic variants was further tested. To examine the potential effect of rare nonsynonymous BST1 variants on the protein structure, we performed in silico structural analysis. Finally, we examined the association of common variants using logistic regression adjusted for age and sex. RESULTS: We found an association between rare heterozygous nonsynonymous variants in BST1 and iRBD (p = 0.0003 at coverage >50× and 0.0004 at >30×), driven mainly by 3 nonsynonymous variants (p.V85M, p.I101V, and p.V272M) found in 22 (1.2%) controls vs 2 (0.2%) patients. All 3 variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare noncoding heterozygous variants in LAMP3 were also associated with iRBD (p = 0.0006 at >30×). We found no association between rare heterozygous variants in the rest of genes and iRBD. Several carriers of biallelic variants were identified, yet there was no overrepresentation in iRBD. CONCLUSION: Our results suggest that rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and to examine whether loss of function of BST1 could be a therapeutic target.

Amplifying the spectrum of SPAST gene mutations.

Hereditary spastic paraplegias (HSPs) include a group of neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities, caused by axon degeneration of corticospinal tracts. Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant form of HSP and is caused by mutations in the SPAST gene. SPAST gene encodes for the protein spastin, a member of the ATPases Associated with a variety of cellular Activity (AAA) family.We describe a newly variant in SPAST gene, within an Italian family affected by pure HSP. In particular, we found a heterozygous intragenic microdeletion of 3T in exon 13 of SPG4 gene. The 3T deletion results in a mutated protein with a unique leucine residues deletion at the protein position 508, in the AAA ATPase domain. This variant is not registered in any public database either as rare normal variant nor as mutation in SPAST gene and the importance of this aminoacid is confirmed by the absolute conservation in multiple alignments with diverse species. We conclude that the novel SPAST gene variant identified is probably pathogenic and destabilizes the precise arrangement of the nucleotide binding domain, with a consequent loss-of-function of the mutated spastin protein.

Epidemiology of paraneoplastic neurological syndromes: a population-based study.

BACKGROUND: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-based incidence study and report the clinical spectrum and antibody profile of PNS in a large area in Northeastern Italy. METHODS: We performed a 9-year (2009-2017) population-based epidemiological study of PNS in the provinces of Udine, Pordenone and Gorizia, in the Friuli-Venezia Giulia region (983,190 people as of January 1, 2017). PNS diagnosis and subgroups were defined by the 2004 diagnostic criteria. Age- and sex-adjusted incidence rates were calculated. RESULTS: We identified 89 patients with a diagnosis of definite PNS. Median age was 68 years (range 26-90), 52% were female. The incidence of PNS was 0.89/100,000 person-years. PNS incidence rates increased over time from 0.62/100,000 person-years (2009-2011), 0.81/100,000 person-years (2012-2014) to 1.22/100,000 person-years (2015-2017). The prevalence of PNS was 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in every 334 cancers in our region. Statistically significant associations were observed between cancer type and Ab-specificity (P < 0.001), and between neurological syndrome and Ab-specificity (P < 0.001). CONCLUSIONS: This first population-based study found an incidence of PNS that approximates 1/100,000 person-years and a prevalence of 4/100,000. Moreover, the incidence of PNS is increasing over time, probably due to increased awareness and improved detection techniques.