Causalgia and complex regional pain syndrome (CRPS) type II with nerve injury can be difficult to treat. Surgical peripheral nerve denervation for causalgia has been largely abandoned by pain clinicians because of a perception that this may aggravate a central component (anesthesia dolorosa).

We selectively searched Pubmed, Cochrane, MEDLINE, EMBASE, CINAHL Plus, and Scopus from 1947 for articles, books, and book chapters for evidence of surgical treatments (nerve resection and amputation) and treatment related to autoimmunity and immune deficiency with CRPS.

Reviews were found for the treatment of causalgia or CRPS type II (n = 6), causalgia relieved by nerve resection (n = 6), and causalgia and CRPS II treated by amputation (n = 8). Twelve reports were found of autoimmunity with CRPS, one paper of these on associated immune deficiency and autoimmunity, and two were chosen for discussion regarding treatment with immunoglobulin and one by plasma exchange. We document a report of a detailed and unique pathological examination of a CRPS type II affected amputated limb and related successful treatment with immunoglobulin.

Nerve resection, with grafting, and relocation may relieve uncomplicated causalgia and CRPS type II in some patients in the long term. However, an unrecognized and treatable immunological condition may underly some CRPS II cases and can lead to the ultimate failure of surgical treatments.

Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2.

This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020–May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement.

One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15–2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46–5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46–3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58–3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08–3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49–5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58–4.82; p < 0.001).

In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Embolization of middle meningeal artery (EMMA) is a relatively new treatment for chronic subdural hematoma (CSDH). To date, an objective method that assesses or describes the extent of EMMA for the treatment of CSDH does not exist. Recently, the concept of a novel grading scale for EMMA in patients with CSDH has emerged. However, this has not been applied to a clinical case setting and inter-rater reliability has not yet been studied. The purpose of this study was to validate the grading scale in clinical practice and to assess for inter-rater reliability.

We retrospectively examined consecutive patients who underwent EMMA for CSDH. Patients were included if the whole head angiogram from common carotid as well as external carotid arteries before and after EMMA were available in the arterial, capillary as well as venous phases. Two independent readers, each with more than 5 years of experience in independent practice, assessed the angiograms for the grading of EMMA and assigned a score ranging between 0 and 3. The grading score between the two readers were compared using Cohen’s Kappa score to assess the inter-rater reliability.

In 19 patients, we found that EMMA had no periprocedural morbidity and mortality. The number of cases in each EMMA grading score category are as follows: 0 n =1; 1 n =3; 2 n =1; and 3 n =10. There was substantial inter-rater reliability for the assessment of grading of EMMA (Kappa = 0.74).

The novel EMMA grading scheme demonstrated substantial inter-rater reliability and appears promising.

Early and effective treatment of central nervous system (CNS) inflammatory disorders is vital to reduce neurologic morbidity and improve long-term outcomes in affected children. Rituximab is a B-cell-depleting monoclonal antibody whose off-label use for these disorders is funded in the province of Alberta, Canada, by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric CNS inflammatory disorders in Alberta.

Rituximab applications for CNS inflammatory indications in patients <18 years of age were identified from the STEDT database between January 1, 2012, and December 31, 2019. Patient information was linked to other provincial datasets including the Discharge Abstract Database, Pharmaceutical Information Network, and Provincial Laboratory data. Analysis was descriptive.

Fifty-one unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis without a specified antibody (n = 16, 31%). Most children were approved for a two-dose (n = 33, 66%) or four-dose (n = 16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets.

The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring. Standardized protocols for the use of rituximab in these disorders and more robust outcome reporting will help better define the safety and efficacy of rituximab in this population

Isocitrate dehydrogenase (IDH) mutation status is a key diagnostic and prognostic feature of gliomas. It is thought to occur early in glioma tumorigenesis and remain stable over time. However, there are reports documenting a loss of IDH mutation status in a subset of patients with glioma recurrence. Here, we identified patients with a documented loss of IDH mutation status longitudinally and performed multi-platform analysis in order to determine if IDH mutations are stable throughout glioma evolution.

We retrospectively identified patients from our institution from 2009 to 2018 with immunohistochemistry (IHC)-recorded IDH mutation status changes longitudinally. Archived formalin-fixed paraffin-embedded and frozen tissue samples from these patients were collected from our institution’s tumour bank. Samples were analysed using methylation profiling, copy number variation, Sanger sequencing, droplet digital PCR (ddPCR) and IHC.

We reviewed 1491 archived glioma samples including 78 patients with multiple IDH mutant tumour samples collected longitudinally. In all instances of documented loss of IDH mutation status, multi-platform profiling identified a mixture of low tumour cell content and non-neoplastic tissue including perilesional, reactive or inflammatory cells.

All patients with a documented loss of IDH mutation status longitudinally were resolved through multi-platform analysis. These findings support the hypothesis that IDH mutations occur early in gliomagenesis and in the absence of copy number changes at the IDH loci and are stable throughout tumour treatment and evolution. Our study highlights the importance of accurate surgical sampling and the role of DNA methylome profiling in diagnostically uncertain cases for integrated pathological and molecular diagnosis.

In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. We tested for vasodilatory reserve by using PETCO2 as the stressor, and Blood Oxygen Level Dependent (BOLD) MRI as a surrogate of blood flow. We correlate the CVR to the incidence of stroke after a 1-year follow-up in patients with symptomatic intracranial SOD.

In this retrospective study, 100 consecutive patients with symptomatic intracranial SOD that had undergone CVR testing were identified. CVR was measured as % BOLD MR signal intensity/mmHg PETCO2. All patients with normal CVR were treated with optimal medical therapy; those with abnormal CVR were offered revascularization where feasible. We determined the incidence of stroke at 1 year.

83 patients were included in the study. CVR was normal in 14 patients and impaired in 69 patients ipsilateral to the lesion. Of these, 53 underwent surgical revascularization. CVR and symptoms improved in 86% of the latter. The overall incidence of stroke was 4.8 % (4/83). All strokes occurred in patients with impaired CVR (4/69; 2/53 in the surgical group, all in the nonrevascularized hemisphere), and none in patients with normal CVR (0/14).

Our study confirms that CO2-BOLD MRI CVR can be used as a brain stress test for the assessment of cerebrovascular reserve. Impaired CVR is associated with a higher incidence of stroke and normal CVR despite significant stenosis is associated with a low risk for stroke.

Frontotemporal dementia (FTD) patients frequently present with psychosis, which complicates diagnosis and management. In this study, we aim to examine the relationship between psychosis and the most common genetic mutations predisposing to FTD, and in the different pathological subtypes of FTD.

We conducted a systematic review, searching the literature up to December 2022, and reviewed 50 articles that met our inclusion criteria. From the reviewed articles, we extracted and summarized data regarding the frequency of psychosis and patient characteristics in each major genetic and pathological subtype of FTD.

Among FTD patients with confirmed genetic mutations or pathological diagnosss, the frequency of psychosis was 24.2%. Among the genetic mutation carriers, C9orf72 mutation carriers had the highest frequency of psychosis (31.4%), whereas GRN (15.0%) and MAPT (9.2%) mutation carriers had lower frequencies of psychosis. MAPT mutation carriers notably developed psychosis at a younger age compared to other genetic groups. The most common psychotic symptoms were delusions among C9orf72 carriers and visual hallucinations among GRN mutation carriers. Among the pathological subtypes, 30% of patients with FUS pathology, 25.3% of patients with TDP-43 pathology, and 16.4% of patients with tau pathology developed psychosis. In the TDP-43 group, subtype B pathology was the most common subtype reported in association with psychosis.

Our systematic review suggests a high frequency of psychosis in specific subgroups of FTD patients. Further studies are required to understand the structural and biological underpinnings of psychosis in FTD.