We describe a 59-year-old male who developed faciobrachial dystonic seizures and serum Anti-LGi1 antibody positivity 5 weeks after subthalamic deep brain stimulation (DBS) implantation for essential ...tremor. Brain MRI prior to implantation was normal. Electroencephalogram was normal. A lung lesion with low PET avidity was identified and biopsied; histology was non-diagnostic. Treatment response to immunoglobulin was observed. Seizures after DBS implantation are rare, and to our knowledge not described in association with anti-LGi1 antibodies.
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•Anti-LGi1 encephalitis identified 5 weeks after deep brain stimulator placement.•Treatment response to immunoglobulin seen with DBS remaining in-situ.•No change in seizure frequency observed with DBS deactivation.
Abstract Genes involved in familial dystonia syndromes (DYT genes) are ideal candidates for investigating whether common genetic variants influence the susceptibility to sporadic primary dystonia. To ...date, there have been few candidate gene studies for primary dystonia and only two DYT genes, TOR1A and THAP1 , have been assessed. We therefore employed a haplotype-tagging strategy to comprehensively assess if common polymorphisms in eight DYT genes ( TOR1A , TAF1 , GCH1 , THAP1 , MR-1 ( PNKD ), SGCE , ATP1A3 and PRKRA ) confer risk for sporadic primary dystonia. The 230 primary dystonia cases were matched for age and gender to 228 controls, recruited from movement disorder clinics in Brisbane, Australia and the Australian electoral roll. All subjects were genotyped for 56 tagging SNPs and genotype associations were investigated. Modest genotypic associations ( P < 0.05) were observed for three GCH1 SNPs (rs12147422, rs3759664 and rs10483639) when comparing all cases against controls. Associations were also seen when the cases were stratified based on presentation. Overall, our findings do not support the hypothesis that common TOR1A variants affect susceptibility for sporadic primary dystonia, and that it is unlikely that common variants around the DYT genes confer substantial risk for sporadic primary dystonia. Further work is warranted to follow up the GCH1 SNPs and the subgroup analyses.
Anti-NMDAR encephalitis most commonly presents to psychiatric services, so early identification of this disorder is essential. We aim to validate the two screening criteria (Scott et al. and Herken ...and Pruss) which have been proposed to identify first episode psychosis patients who should have anti-NMDAR antibody testing. The performance of the screening criteria were assessed using anti-NMDAR encephalitis cases published in the literature, and antibody positive and negative cases from a state-wide cohort (Queensland, Australia). Sensitivity, specificity and area under receiver operator characteristic curve analysis was performed. There were 258 anti-NMDAR encephalitis cases and 103 control cases, which demonstrated high performance of both Scott et al. “screening recommended” criteria (sensitivity 97.3%, specificity 85.4%, AUC 0.914) and Herken and Pruss “yellow flags” criteria (sensitivity 91.5%, specificity 83.5%, AUC 0.875). These criteria remained accurate when neurological variables were excluded, and in cases without psychosis. The Scott et al. “screening not recommended”, and Herken and Pruss “red flags” criteria did not demonstrate clinical utility for first episode psychosis case screening. The screening criteria with good performance identify an atypical picture of psychiatric presentation with increased risk of anti-NMDAR positivity prior to overt neurological symptoms or investigations and may be beneficial to include in the routine psychiatric assessment process.
•Screening criteria for anti-NMDAR encephalitis demonstrates high clinical utility.•Screening criteria remain accurate without neurological symptoms or investigations.•Anti-NMDAR encephalitis screening should form part of routine psychiatric assessment.
ObjectivesTo characterise functional brain activity reflecting neuropsychiatric disturbances in patients with anti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis.Methods12 anti-NMDA-R ...encephalitis patients and 19 age and gender matched control participants completed neuropsychological tests including Hopkins Verbal Learning Test, Digit Span test, logical memory subtests 1 and 2 from the Wechler Memory Scale, National Adult Reading Test of IQ, Stroop test, Trail making tests A&B, Verbal fluency, matrix reasoning and WAS-II Vocabulary subtest. Functional Magnetic Resonance Imaging (fMRI) of brain function was undertaken in each participant while undergoing the Shifting Response Set task.ResultsSignificant differences in neurocognitive function were observed, with decreased function in anti-NMDA-R encephalitis patients on tests of verbal fluency (F1,29=6.7, p=0.15) backwards digit span recall (F1,29=4.9, p=0.035), Hopkins verbal learning test (F1,29=16.5, p<0.001) matrix reasoning test (F1,29=9.7, p=0.004), vocabulary (F1,29=16.8, p<0.001), trail making test (F1,29=9.0, p=0.006) and logical memory (F1,29=6.3, p=0.018). Factor analysis revealed these neurocognitive tests loaded onto a single factor, providing one statistical measure quantifying deficits across these domains.Functional brain responses during shifting response set differed significantly between anti-NMDA-R encephalitis patients and matched controls. Whereas controls reduced activity within the subgenual cingulate, ventrolateral and superior frontal prefrontal cortices, activity was increased within patients.Neural responses in the right superior parietal cortex, mid anterior cingulate cortex and right ventrolateral cortex reflected generalised neurocognitive deficits (single factor) in patients, relative to controls.ConclusionsOur findings further understanding of neural changes within anti-NMDAR encephalitis, and identify cortical regions where altered function reflects the severity of neurocognitive deficits.
The authors examined and compared the clinical presentation of CSF positive and negative
-methyl-d-aspartate receptor (NMDAR) antibody.
The investigators performed a retrospective chart review of ...NMDAR-antibody-positive cases (serum or CSF) involving patients presenting to psychiatric services from 2010 to 2018 in Queensland, Australia. Presentation, progress, investigations, and efficacy of treatment are detailed.
There were 24 serum or CSF NMDAR-antibody-positive cases and three equivocal serum results. High rates of prodromal cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity were observed in the 16 CSF NMDAR-antibody-positive case patients and two CSF NMDAR-antibody-negative case patients, all evident before neurological deterioration with seizures, movement disorder, and autonomic disturbance occurring in the weeks following admission. The majority of these patients (N=17) were treated successfully with immunomodulatory therapy. The nine remaining patients, who were CSF NMDAR antibody negative or equivocal, did not demonstrate any of these features and improved with psychiatric care alone.
These findings suggest that traditional psychiatric care may be appropriate for patients with isolated psychiatric symptoms who have positive serum NMDAR testing when CSF is negative and there are no key clinical features such as cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity. However, if these key features are present, a trial of immunomodulatory treatment should be considered with repeated examination of CSF for neuronal antibodies.
Introduction: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated neurological disorder that (among other severe neuropsychiatric symptoms) affects cognition. This study ...aimed to summarize current knowledge regarding the rates, nature, and predictors of neuropsychological dysfunction in patients recovering from anti-NMDAR encephalitis. Method: A systematic review of studies describing neuropsychological outcomes following anti-NMDAR encephalitis was conducted. Electronic databases Medline, PsycINFO, EMBASE, and CINAHL were searched from inception to September 2016. Results were summarized using descriptive statistics and a series of chi-square analyses. Results: Of 4030 identified studies, 44 were included. These reported neuropsychological outcomes for 109 treated patients (83.5% female, M
age
= 22.5 years, range = 2-67) recovering from anti-NMDAR encephalitis. High rates of neuropsychological dysfunction were identified, with diverse impairments of variable severity documented in >75% of patients at assessments conducted during acute, subacute, and longer term recovery periods. Despite this, cognitive outcomes were ultimately considered favorable in most cases (74.3%). This estimate does not account for the potential impact of relapses. The frequency of impairments in overall intellectual functioning, language, attention, working memory, and visuospatial functions were significantly higher within the acute recovery period than in later phases of convalescence. However, rates of impaired processing speed, episodic memory, and aspects of executive functioning were consistent across time points. Adverse neuropsychological outcomes occurred at significantly higher frequency in patients where immunotherapy was delayed, χ
2
(1, N = 66) = 10.84, p < .003. Conclusions: Neuropsychological deficits are prevalent at all points of recovery from anti-NMDAR encephalitis, although improvement in cognitive outcomes can be expected as patients recover. Some cognitive deficits may be less likely than others to resolve. Close neuropsychological monitoring is warranted in this population. Longitudinal studies of neuropsychological functioning of patients with anti-NMDAR encephalitis are needed to accurately inform prognosis.
Background
Anti‐N‐methyl‐D‐aspartate‐receptor (anti‐NMDA‐R) encephalitis is a complex autoimmune neuropsychiatric syndrome. Although initially associated with ovarian teratoma, subsequent studies ...have demonstrated that anti‐NMDA‐R encephalitis may occur without an identifiable cause or be triggered by viral infection of the central nervous system such as herpes simplex virus encephalitis (HSVE).
Aim
To present details from a Queensland cohort analysing triggering events in patients with anti‐NMDA‐R encephalitis in an Australian context.
Methodology
The authors identified patients with anti‐NMDA‐R encephalitis diagnosed and managed through public hospitals in Queensland, Australia, between 2010 and the end of 2019. Data collected included demographics, clinical presentation, investigation results, management and outcome measurements.
Results
Thirty‐one cases of anti‐NMDA‐R encephalitis were included in the study. Three cases of anti‐NMDA‐R encephalitis were triggered by prior HSVE, five cases were associated with ovarian teratoma and 23 cases had no identifiable trigger. There were an additional three cases in which anti‐NMDA receptor antibodies were present in the context of other disease states but where the patient did not develop anti‐NMDA‐R encephalitis. Cases triggered by HSVE or associated with ovarian teratoma experienced a more severe disease course compared to cases with no identifiable trigger. All groups responded to immunosuppressive or immunomodulatory therapy. Analysis of clinical characteristics revealed a complex heterogeneous syndrome with some variability between groups.
Conclusion
In this cohort, the number of cases of anti‐NMDA‐R encephalitis triggered by HSVE is comparable to those triggered by ovarian teratoma. However, the majority of cases of anti‐NMDA‐R encephalitis had no identifiable trigger or associated disease process.
SOX1 antibodies are generally associated with small cell lung cancer and anti-Hu antibody overlap is common. This case demonstrates isolated anti-SOX1 antibodies with an uncommon tumor type, and ...relapse of a paraneoplastic syndrome with recurrence of tumor.
We describe a case of a 65-year-old male with a paraneoplastic peripheral neuropathy and anti-SOX1 antibody positivity in the context of a prior male breast Grade 2 ductal carcinoma, in remission at the time of the initial neurological presentation.
Treatment response to intravenous immunoglobulin (IVIg) was demonstrated. After period of clinical stability on IVIg in the context of remission of breast carcinoma, the patient experienced a relapse of his neuropathy. This was associated with tumor recurrence and again responded to tumor excision, radiotherapy and IVIg.
Male breast carcinoma has not previously been associated with anti-SOX1 antibody positive paraneoplastic neuropathy.
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•Immune mediated neuropathies are an increasingly recognized paraneoplastic phenomenon.•This case is a reminder that worsening of a paraneoplastic syndrome should prompt search for underlying tumor recurrence.•Treatment with immunoglobulin may provide benefit in immune mediated neuropathies associated with the anti-SOX1 antibody.
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