UNASSIGNED: First reports associated mutations in triggering receptors expressed on myeloid cells 2 (TREM2) with autosomal recessive Nasu-Hakola disease characterized by painful bone cysts and progressive presenile dementia with psychotic symptoms; however, recent TREM2 biallelic rare variants are suggested to be causative also for the behavioral variant of frontotemporal dementia (bvFTD) without bone involvement.
UNASSIGNED: Clinical data of three unrelated bvFTD patients carrying TREM2 biallelic variants were evaluated. All patients underwent neurological, psychiatric, and cognitive evaluation and neuroimaging. A full neuropsychological assessment was performed in two cases.
UNASSIGNED: Two patients carried compound heterozygous TREM2 variants, p.R62C and p.T66M, and one carried the homozygous p.D87N variant. Based on all obtained clinical and neuroimaging data, a behavioral variant of frontotemporal dementia was diagnosed in all cases. Their clinical manifestation was typical with neuropsychiatric and cognitive features, without bone abnormalities.
UNASSIGNED: Despite all three subjects partially resembling clinical manifestations of Nasu-Hakola disease with TREM2 mutations, we reveal some distinct features, including age of onset, neuroimaging findings, or disease course.

OBJECTIVE: This study aimed to assess the neuroimaging abnormalities and their progression in patients with Subacute sclerosing panencephalitis (SSPE) and identify clinical predictors of these imaging findings.
METHODS: This prospective observational study evaluated clinical and neuroimaging features in patients with SSPE. Patients were categorized using Dyken\'s criteria, Jabbour\'s staging system, and the definition of fulminant SSPE. They underwent comprehensive clinical assessments, cerebrospinal fluid examination, Electroencephalogram (EEG), and Magnetic Resonance Imaging (MRI) scans. Treatment involved intrathecal interferon‑α and antiepileptic medications. Functional disability was assessed using the modified Barthel index. Follow-ups were performed at 6 months, including reassessment of Modified Barthel Index (MBI) and Jabbour\'s staging and EEG and MRI scans.
RESULTS: The mean age was 13.9 ± 6.7 years, with males comprising 81.5% (44/54) of the cohort. Fulminant SSPE was noted in 33% (18/54) of cases. Disease duration before presentation varied significantly between fulminant and non-fulminant forms (p = 0.001). Neuroimaging abnormalities were more prevalent in JS III stage patients, with diffuse cerebral atrophy being a significant finding (p = 0.011). Basal ganglia involvement correlated with movement disorders. The 6‑month follow-up showed increased cerebral atrophy (p = 0.004). Increasing disease duration was an independent predictor of cerebral atrophy. An Intercomplex interval (ICI) of more than 10 minutes correlated with normal neuroimaging, 10 patients died within the study period, 8 of whom had fulminant SSPE.
CONCLUSIONS: Parieto-occipital White matter hyperintensity (WMH) is the most prevalent and sensitive neuroimaging finding for the diagnosis of SSPE. Despite interferon treatment, cerebral atrophy progressed in both aggressive and fulminant SSPE. Increasing disease duration is an independent predictor of cerebral atrophy.

Isolated-subsegmental-pulmonary-embolism (SSPE) is increasingly diagnosed with the use of computed-tomography-pulmonary-angiogram (CTPA). There remains clinical equipoise for management of SSPE with previous studies not accounting for frailty while determining clinical outcomes. Clinical outcomes among patients with isolated SSPE were compared with those with a more proximal PE after accounting for frailty and other risk-factors. This study included all patients with a positive CTPA for pulmonary embolism (PE) admitted between 2017 and 2021 to two Australian-tertiary-hospitals. Frailty was determined by use of the hospital-frailty-risk-score (HFRS). Competing-risk-analysis and Cox-proportional hazard models determined the cumulative-risk of VTE and mortality within 3 months and 1 year of index PE event after adjustment for frailty and other variables. Of 334 patients with positive CTPA for PE, 111 (33.2%) had isolated-SSPE. The mean (SD) age was 64.3 (17.7) years, 50.9% were males and 9.6% were frail. The risk of recurrent VTE within 3-months (0.9% vs. 1.8%, P = 0.458) and within 1-year of follow-up (2.7% vs. 6.3%, P = 0.126) did not differ significantly between patients with isolated SSPE and those with more proximal PE. After adjusted analyses, the cumulative-incidence of recurrent VTE was not different among patients with isolated SSPE within 1 year of index event [subdistribution-hazard-ratio (HR) 0.84, 95% CI 0.19 to 3.60]. Similarly, mortality within 1 year of index event was also not different between the two groups (aHR 1.72, 95% CI 0.92-3.23). The prevalence of SSPE was 33.2% and even after adjustment for frailty these patients had no different clinical outcomes than those with proximal PE.

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective of this case-control study was to analyse the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken\'s criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour\'s system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (±6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour\'s first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells, and cytotoxic T-cells were significantly higher in cases. IgG, IgM, and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favorable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to correlate significantly with favorable outcome. Immune-dysregulation may play a significant role in shaping one\'s response to measles infection as well as in determining vaccine-efficacy.

BACKGROUND: The incidence of subsegmental pulmonary embolism (SSPE) has increased with improvements in imaging technology. There is clinical equipoise for SSPE treatment, with conflicting evidence of improved mortality or reduced venous thromboembolism recurrence with anticoagulation. SSPE studies have significant heterogeneity and often lack adequately matched disease comparator groups.
OBJECTIVE: To determine the prevalence, management, and outcomes of SSPE and compare them to patients with main, lobar, segmental, and no pulmonary embolism (PE).
METHODS: All adult patients undergoing CT pulmonary angiography (CTPA) between 2013 and 2019, at 3 UK hospitals were included in the study. CTPA reports were text mined for language relating to PE, and then further manually screened for the presence and anatomical location of PE. Patient groups were propensity matched by age, sex, and year of CTPA prior to analysis. 3-month outcomes of major bleeding, VTE recurrence, and death were recorded.
RESULTS: 79 (3.8%) SSPEs were identified from 2,055 diagnoses of PE, and 14,300 CTPA reports. 44 (56%) of SSPEs were single artery emboli, 25 (32%) were multiple unilateral emboli, and 10 (13%) were multiple bilateral emboli. Mortality, VTE recurrence and major bleeding were similar at 3 months across all groups. 87.3% of SSPE imaging reports had an additional radiological diagnosis, with pleural effusion (30%), consolidation (19%), and cardiomegaly (19%) being the most common.
CONCLUSIONS: The prevalence of SSPE was 3.8% of all PEs and there were a substantial number of additional radiological findings in the SSPE group that may have accounted for their symptoms.

UNASSIGNED: Subacute Sclerosing Pan Encephalitis (SSPE) may present with atypical clinical features and lead to diagnostic dilemma. Conventional magnetic resonance imaging (MRI) may be normal in early stage of SSPE.
UNASSIGNED: The aim of this work was to study the demography, clinical profile including atypical features of SSPE patients, and the utility of diffusion tensor imaging (DTI) as an adjunctive diagnostic tool to the anti-measles antibody and conventional MRI.
UNASSIGNED: Consecutive 25 patients of SSPE were included. Clinical details were recorded at baseline and 6 months follow-up. Anti-measles antibody in serum and CSF, CSF/Serum Quotient reference (CSQ ref), and radiological details including comparison of DTI between SSPE patients and controls were also noted.
UNASSIGNED: Of 25 patients, 17 (68%) were male. The most common presenting feature at onset was myoclonus with or without falls (13, 52%). Atypical features such as seizure, hemiparesis, and visual problems were present in 28% patients. At 6 months, 9 patients had progressive course (6 expired), 10 were static, and 6 lost to follow-up. MRI was normal in 8 (32%) patients (stage 2/3- 7/1). On comparison between SSPE patients (N = 10) and control (N = 10) groups, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) values were reduced and elevated, respectively, at most of the regions of interest with significant difference at many sites.
UNASSIGNED: A significant number of patients (28%) had atypical features at onset. DTI is an adjunctive tool which supplements the conventional MRI and increase diagnostic yield. It may be a future option to assess disease progression and treatment response.

Background: Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised by myoclonus, seizures, and neuropsychiatric issues. Movement disorders apart from myoclonus are reportedly uncommon. We aimed to describe frequency and proportion of movement disorders among children with subacute sclerosing panencephalitis, hypothesizing that these occur more frequently than previously reported. Methods: In this cross-sectional study, we enrolled children with subacute sclerosing panencephalitis between 1 month and 18 years of age who fulfilled the diagnosis of subacute sclerosing panencephalitis as per modified Dyken criteria, and examined them for movement disorders. We also assessed their clinical profile and disease severity via Jabbour staging and modified Rankin Scale score. We compared demographic, clinical, and laboratory features of children with and without movement disorders. Results: We enrolled 50 children (36 males; 72%) (age range 1.5-14 years). Of these, 28 (56%) had movement disorders. Among movement disorders, the most frequent was myoclonus (92%), followed by ataxia (9; 18%), chorea-athetosis (7; 14%), dystonia (6; 12%), tremor (4; 8%), repetitive behavior (4; 8%), and parkinsonism (3; 6%). Movement disorders were the presenting feature of subacute sclerosing panencephalitis among 7 children. There were no significant differences in clinical or laboratory features among children with and without movement disorders. Conclusions: Movement disorders were frequent in subacute sclerosing panencephalitis. Hyperkinetic disorders were dominant. Dystonia and chorea-athetosis occurred more commonly among nonmyoclonus movement disorders. Movement disorders may manifest even in earlier stages of subacute sclerosing panencephalitis and may be the heralding feature. Recognition of these features is important to plan management and reduce morbidity.

Aprepitant is a neurokinin-1 receptor antagonist approved for the treatment of chemotherapy-induced nausea. We aimed to investigate the safety and efficacy of aprepitant in patients with subacute sclerosing panencephalitis.
A randomized, double-blind, placebo-controlled study was conducted in patients with subacute sclerosing panencephalitis assigned to receive two courses of aprepitant 250 mg/day orally or placebo for 15 days with an interval of two months between courses. Primary end points were safety and tolerability, and secondary end point was clinical improvement or stabilization assessed by subacute sclerosing panencephalitis scoring system. Electroencephalography (EEG), brain magnetic resonance imaging, and cerebrospinal fluid measles-specific immunoglobulin G index were evaluated before and after treatment.
Sixty-two patients with subacute sclerosing panencephalitis were allocated to aprepitant (n = 31, median age 18 years) or placebo (n = 31, median age 22 years) group. Fifteen patients left the study within the first six months and 12 patients left between six and 12 months. Aprepitant was well tolerated and treatment-associated adverse events were similar to those described in the treatment of nausea. Clinical status at six and 12 months\' follow-up did not differ between aprepitant and placebo groups. Post-treatment EEG scores at 12 months were better in the aprepitant group (P = 0.015). Cerebral atrophy on magnetic resonance imaging increased in both groups, whereas measles-specific immunoglobulin G index decreased in the placebo group.
In this first clinical trial of aprepitant treatment in patients with subacute sclerosing panencephalitis, the drug was safe and well tolerated. No clinical effect was observed. A modest improvement in EEG findings might justify trials for longer periods because EEG changes can precede clinical findings in subacute sclerosing panencephalitis.

To study the different epilepsy syndromes that included epileptic spasms (ES) in clusters without hypsarrhythmia (WoH).
Between 2/1990 and 7/2013, we registered 48 patients with the electroclinical diagnostic criteria of ES in clusters WoH.
We recognized two subgroups. In the first subgroup of 30 patients, ES started at a mean age of 10.6 months (range, 2-40 months). Ictal EEG recordings showed diffuse high-amplitude slow waves in 15 patients, diffuse slow waves followed by voltage attenuation in six patients, diffuse fast rhythms in five, diffuse slow waves with superimposed fast rhythms in three, and diffuse sharp waves in one. In the second subgroup of 18 patients, nine had electroclinical features of Lennox-Gastaut syndrome, four had epilepsy with myoclonic and atonic seizures, two had Dravet syndrome, one 6-year-old boy had a non-convulsive status epilepticus characterized by atypical absences associated with ES, one had epilepsy with migrating seizures of infancy, and one patient had clinical features of subacute sclerosing panencephalitis with ES. ES started at a mean age of 6.3 years (range, 0.5-13 years). The ictal EEG recording during the ES showed diffuse fast rhythms in 10 cases, diffuse slow waves with superimposed fast rhythms in four, and diffuse slow waves in four.
Our study shows two subgroups of children with ESWoH. The first subgroup had a well-defined electroclinical syndrome predominantly in infancy, and in the second subgroup ES was one more seizure type associated with an epileptic encephalopathy other than West syndrome predominantly occurring in childhood.

OBJECTIVE: The previously reported functional mutation rs75932628-T (p.R47H) in the triggering receptor expressed on myeloid cells 2 (TREM2) is a genetic risk factor for Alzheimer\'s disease, Parkinson\'s disease (PD) and frontotemporal dementia, in European populations. This study aims to assess the genetic association of the variant rs75932628-T with PD and leucoaraiosis (LA) in a Han Chinese population.
METHODS: This population-based study was conducted in China by Xiamen University and its affiliated hospital.
METHODS: 308 patients with LA, 342 patients with PD and 198 healthy blood donors were recruited from the First Affiliated Hospital of Xiamen University.
METHODS: Genotyping was performed by molecular beacon real-time PCR and Sanger sequencing.
RESULTS: None of our participants carried the rs75932628-T mutation.
CONCLUSIONS: Our results corroborate and extend previous findings, concluding that the variant rs75932628-T (p.R47H) in TREM2 is not a risk factor for LA or PD in the Han Chinese population.