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Modern management of MS targets No Evidence of Disease Activity (NEDA): no clinical relapses, no magnetic resonance imaging (MRI) disease activity and no disability worsening. While MRI is the principal tool available to neurologists for monitoring clinically silent MS disease activity and, where appropriate, escalating treatment, standard radiology reports are qualitative and may be insensitive to the development of new or enlarging lesions. Existing quantitative neuroimaging tools lack adequate clinical validation. In 397 multi-center MRI scan pairs acquired in routine practice, we demonstrate superior case-level sensitivity of a clinically integrated AI-based tool over standard radiology reports (93.3% vs 58.3%), relative to a consensus ground truth, with minimal loss of specificity. We also demonstrate equivalence of the AI-tool with a core clinical trial imaging lab for lesion activity and quantitative brain volumetric measures, including percentage brain volume loss (PBVC), an accepted biomarker of neurodegeneration in MS (mean PBVC −0.32% vs −0.36%, respectively), whereas even severe atrophy (>0.8% loss) was not appreciated in radiology reports. Finally, the AI-tool additionally embeds a clinically meaningful, experiential comparator that returns a relevant MS patient centile for lesion burden, revealing, in our cohort, inconsistencies in qualitative descriptors used in radiology reports. AI-based image quantitation enhances the accuracy of, and value-adds to, qualitative radiology reporting. Scaled deployment of these tools will open a path to precision management for patients with MS.

IntroductionMRI-guided focused ultrasound (MRgFUS) thalamotomy provides an exciting development in the field of minimally invasive stereotactic neurosurgery. Current treatment options for focal hand dystonia are limited, with potentially more effective invasive stereotactic interventions, such as deep brain stimulation or lesional therapies, rarely used. The advent of minimally invasive brain lesioning provides a potentially safe and effective treatment approach with a recent pilot study establishing MRgFUS Vo-complex thalamotomy as an effective treatment option for focal hand dystonia. In this study, we undertake an open-label clinical trial to further establish MRgFUS Vo-complex thalamotomy as an effective treatment for focal hand dystonia with greater attention paid to potential motor costs associated with this treatment. To elucidate pathophysiology of dystonia and treatment mechanisms, neurophysiological and MRI analysis will be performed longitudinally to explore the hypothesis that neuroplastic and structural changes that may underlie this treatment benefit.Methods and analysisA total of 10 participants will be recruited into this open-label clinical trial. All participants will undergo clinical, kinemetric, neurophysiological and radiological testing at baseline, followed by repeated measures at predesignated time points post MRgFUS Vo-complex thalamotomy. Further, to identify any underlying structural or neurophysiological abnormalities present in individuals with focal hand dystonia, 10 age and gender matched control participants will be recruited to undergo comparative investigation. These results will be compared with the intervention participants both at baseline and at 12 months to assess for normalisation of these abnormalities, if present.Ethics and disseminationThis trial was reviewed and approved by the St Vincent’s Health Network Sydney Human Research Ethics Committee (2022/ETH00778). Study results will be published in peer-reviewed journals and presented at both national and international conferences.Trial registration numberCTRN12622000775718.

ObjectivesTo report the long-term outcomes in Tremor-Dominant Parkinson Disease (TDPD) after a unilateral Focused Ultrasound (FUS) thalamotomy; and explore factors that may predict the outcome.MethodRetrospective blinded video assessment of consecutive TDPD patients who underwent a unilateral FUS thalamotomy was undertaken. Patients were classified into two groups: ‘responder’ (R) (>50% improvement in Hand Tremor Score at last follow-up) or ‘suboptimal responder’ (SR) (<50% improvement in HTS). Patient and treatment parameters were compared between the two groups.ResultsFrom November 2018, to February 2023, 17 patients with TDPD underwent a unilateral FUS thalamotomy at our centre. Pre- and post-operative videos were available in 15 patients for analysis (age 71.5±6.3 y.o, disease duration 7.3±8.0 years, baseline HTS 12.7±5.5, follow-up 18.7±13.7 months). The R group included 7 patients with a HTS of 1.7±1.5 at the last follow-up (19.7±13.9 months), compared to 8 patients in the SR group, with a HTS of 16.5±9.9 at a mean follow-up time of 14.3±13.7 months. There were no baseline differences between the groups. Tremor in the untreated hand was greater in the SR’s compared to R’s following treatment (8.9±5.4 vs. 1.3±1.9, p<0.001).ConclusionIn the long-term, unilateral FUS thalamotomy for TDPD improved tremor by greater than 50% in approximately a half of patients. Baseline clinical features and treatment parameters, including thalamotomy lesion volume did not predict the ‘responder’ from ‘suboptimal responder’ groups. Suboptimal long-term response may be related to progression of Parkinson’s disease, in these patients.

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.MethodsThis study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.OutcomesThe primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.ResultsThirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12–66). The median Expanded Disability Status Scores (EDSS) was 6 (2–7) and patients had failed a median of 4 (2–7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+ T regulatory cells, immunosuppressive CD56hi natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT.ConclusionsThe EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.Trial registration numberACTRN12613000339752.

In the context of an emerging Japanese encephalitis outbreak within Australia, we describe a novel locally acquired case in New South Wales. A man in his 70s had rapidly progressive, fatal meningoencephalitis, diagnosed as caused by Japanese encephalitis virus by RNA-based metagenomic next-generation sequencing performed on postmortem brain tissue.

ObjectiveTo investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model.MethodsWe monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint; change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints.ResultsIn patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p<0.01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p<0.001), and driven by an early improvement, in both patients and HC.ConclusionWe found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a ‘permissive’ local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.

There is increasing evidence that the spectrum of human polyomavirus 2 (JCV) CNS disease includes novel syndromes other than progressive multifocal leukoencephalopathy (PML), the appreciation of which is increasingly important in the context of MS therapies and immunodeficiency states. Our objective is to describe unusual presentations of JCV infection to heighten clinician awareness. We describe three case reports of various PML presentations. Firstly a 56-year-old HIV positive male with decades of viral suppression and normal immune function presented with 1 month of non-specific headache that spontaneously resolved despite an MRI showing a new area of PML and CSF being JC DNA + . He had had two similar episodes in 2013 and 2014 with MRI scans consistent with PML, CSF, JCV, and PCR positivity once and brain biopsy-positive twice. Another 61-year-old male presented with subacute binocular vision loss and was found to have newly diagnosed HIV and JCV DNA detected in CSF. MRI brain only demonstrated symmetrical chiasmo-hypothalamic enhancement. There has been some improvement with combination antiretroviral therapy and corticosteroids for immune reconstitution inflammatory syndrome (IRIS). Thirdly, a 65-year-old male presented with subacute progressive confusion and behavioural disturbance, one year post-bilateral lung transplantation. MRI brain demonstrated no evidence of PML but CSF on three occasions demonstrated a progressively increasing JCV DNA load. Despite reduction in his immunosuppression, the patient developed profound encephalopathy without localising features leading to death two months later. These cases emphasise the atypical presentations of JCV: chronic relapsing, unusual symmetrical visual pathway disease, and non-localising encephalopathy without MRI evidence of PML.

IntroductionCervical dystonia is the most common form of focal dystonia in adults. Both isolated and segmental forms of cervical dystonia respond to stereotactic neurosurgical intervention with either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS). Whilst the outcomes relating to the improvement in dystonia severity, disability and pain are comparable between GPi and STN targeting, GPi DBS can be complicated by the development of stimulation-induced bradykinesia with reports of secondary failure in dystonia control.CaseWe describe the case of a 67-year-old female with a fourteen-year history of medically refractory segmental dystonia (cervical/facial/oromandibular) who underwent bilateral STN DBS insertion, nine years after initial GPi DBS surgery, due to the development of bradykinesia and partial secondary failure of dystonia control. Following the addition of STN electrodes, there was improvement cervical dystonia at one week maintained through early follow up at six weeks. GPi DBS was continued, but at a lower amplitude, with improved gait and reduced stimulation-induced bradykinesia.ConclusionVarious treatment approaches have been described for the management of secondary failure of GPi DBS in cervical dystonia, including botulinum toxin, additional GPi electrodes and STN DBS with, or without, pallidotomy. This case highlights the safety and efficacy of rescue bilateral STN electrode insertion for the management of bradykinesia and partial secondary failure of GPi DBS in segmental cervical dystonia, with early benefit using combined STN and GPi DBS. Longer follow-up in a larger number of patients is required to ensure the long-term effectiveness of this approach.

BackgroundLeptospirosis, a zoonotic infection caused by Leptospira species, is a rare cause of neurological complications, including meningitis, encephalitis, and intracranial haemorrhage. Subdural haemorrhage (SDH) in leptospirosis is exceptionally rare, with fewer than ten cases reported worldwide. This case highlights an unusual presentation of neuroleptospirosis with atraumatic, bilateral SDH exhibiting irregular, loculated morphology, and a review of the limited literature shows a unique tendency of neuroleptospirosis (especially icterohaemorrhagic leptospirosis) to cause such morphologically unusual spontaneous subdural haematomas.ResultsA 60-year-old woman from rural New South Wales presented with fever, hypotension, renal failure, and cholestatic liver failure, necessitating continuous renal replacement therapy and vasopressor support. On hospital day 11, she developed multiple left hemibody focal motor seizures. Imaging revealed acute, spontaneous, bilateral asymmetrical subdural hematomas with an irregular, loculated appearance and midline shift. Serological testing confirmed acute leptospirosis (IgM and IgG positive). She improved well with ceftriaxone/doxycycline, antiepileptic medication treatments and supportive care for renal and hepatic dysfunction, and serial imaging demonstrated gradual improvement of the subdural haematomas. A review of literature revealed similar unusual morphologies in the few reported cases of neuroleptospirosis-associated subdural haemorrhages.ConclusionNeuroleptospirosis should be considered in the differential diagnosis of atraumatic SDH, especially in patients with epidemiological risk factors. Such SDH is often noticeably irregular in shape with internal heterogeneity, reflecting the systemic coagulopathy, endothelial dysfunction, vasculitis and direct bacterial invasion that pathogenetically underlie the haemorrhagic complications of leptospirosis. Early serological testing and multidisciplinary management are critical to optimising outcomes in this rare but severe complication.