Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

BACKGROUND AND OBJECTIVES: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. METHODS: Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. RESULTS: A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. DISCUSSION: Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Resective epilepsy surgery and its impact on depression in adults: a systematic review, meta-analysis, and implications for future research.

BACKGROUND: How epilepsy surgery influences the bidirectional relationship of epilepsy and depression remains poorly defined. METHOD: For a better understanding of this question, we conducted a systematic review and meta-analysis of risk ratio on depression prevalence before and after epilepsy surgery, using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Three databases were comprehensively screened for all studies assessing depression before and after resective surgery in adult epileptic patients until 8 October 2022. Studies were included if depression was assessed before and after epilepsy surgery regardless of the time of follow-up. A total of 1917 studies were screened for eligibility and 91 full-texts up for inclusion; 35 studies were finally included, 25 studies and 2563 patients were included in main meta-analysis and 10 for exploratory analysis. Risk of bias was assessed using Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) from Cochrane. To derive the pooled depression rates before and after surgery, a meta-analysis with inversed-variance was performed using random-effects logistic models with Peto's correction and a 95% CI. Heterogeneity was assessed with Cochran's Q-test along with its derived measure of inconsistency I2. RESULTS: Overall, the depression rates before and after resective epilepsy surgery were 0.70 (0.53 to 0.91) 95% CI, suggesting that the rate of depression at last follow-up evaluation tends to decrease after Resective Epilepsy Surgery (RES). Subgroup analysis suggest a positive long-term effect appears with a significant lower rates of depression already 6 months (0.61 (0.38 to 0.98)), after surgery which is maintained over time after 1 year (0.53 (0.31 to 0.90)), and after 2 years (0.62 (0.42 to 0.92)). CONCLUSION: This important finding should be taken in consideration before resective surgery for drug-resistant epilepsies. However, prospective studies should be conducted to characterise which patient, at the individual level, might be at risk of de novo or worsening of depression. PROSPERO REGISTRATION NUMBER: CRD42022355386.

Revisiting anti-Hu paraneoplastic autoimmunity: phenotypic characterization and cancer diagnosis.

Anti-Hu are the most frequent antibodies in paraneoplastic neurological syndromes, mainly associated with an often limited stage small cell lung cancer. The clinical presentation is pleomorphic, frequently multifocal. Although the predominant phenotypes are well characterized, how different neurological syndromes associate is unclear. Likewise, no specific study assessed the performance of new-generation CT and PET scanners for cancer screening in these patients. Herein, we aimed to describe the clinical pattern and cancer screening in a retrospective cohort of 466 patients with anti-Hu autoimmunity from the French Reference Centre on Paraneoplastic Neurological Syndromes registry. Clinical presentation, cancer screening and diagnosis were analysed. Among the 466 patients, 220 (54%) had multifocal neurological involvement. A hierarchical cluster analysis grouped the patients into (i) mainly limbic encephalitis, (ii) predominantly peripheral neuropathy and (iii) broad involvement of the nervous system (mixed group). Compared with limbic encephalitis and mixed groups, patients in the neuropathy group more frequently had a chronic onset of symptoms (29 versus 13 and 17%), elevated CSF proteins (83 versus 47 and 67%) and died from cancer progression (67 versus 15 and 28%; all P < 0.05). No significant difference in overall survival was observed between groups. Dysautonomia and brainstem signs were associated with a higher risk of death from the neurological cause; cancer diagnosis was the main predictor of all-cause death, especially when diagnosed within 2 years from clinical onset (all P < 0.05). Three hundred and forty-nine (75%) patients had cancer: in 295 (84%) neurological symptoms preceded tumour diagnosis, being lung cancer in 262 (89%), thereof small cell lung cancer in 227 (87%). First CT scan revealed lung cancer in 205/241 (85%), and PET scan shortened the interval to diagnosis when the initial CT scan was negative [7 months (1-66) in 27 patients versus 14 months (2-45) in 6; P < 0.001]. Although cancer diagnosis mostly occurred within 2 years from clinical onset, 13/295 (4%) patients exceeded that threshold. Conversely, 33 patients (7%) were 'cancer-free' after 2 years of follow-up. However, 13/33 (39%) had initial suspicious imaging findings that spontaneously regressed. In conclusion, although anti-Hu autoimmunity clinical presentation is mostly multifocal, we observed patients with a predominant limbic syndrome or isolated sensory neuropathy. Early implementation of PET scan shortens the interval to cancer diagnosis, which was the strongest predictor of death, especially if diagnosed ≤2 years from clinical onset. As cancer was diagnosed >2 years after clinical onset in few patients, screening should be extended up to 5 years. In addition, tumour regression was suspected in a substantial proportion of 'cancer-free' patients.

Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines. OBJECTIVES: Our study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model. METHODS: Data on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually. RESULTS: 90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27-47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC. CONCLUSION: We obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.

Focal inhibitory seizure with prolonged deficit in adult Sturge-Weber syndrome.

Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder often related to varying degrees of motor impairment. The phenomenon of prolonged ictal paresis is a rare seizure sign that can be due to lesions affecting the centro-parietal lobe. Focal inhibitory motor seizures can be difficult to differentiate from other clinical entities such as stroke, migraine or postictal paresis. We describe the case of a 40-year-old patient suffering from Sturge-Weber syndrome, admitted due to prolonged right-sided hemiparesis following a usual seizure. Repeated EEGs during the prolonged deficit showed only intermittent left fronto-parietal sharp waves. (99m)Tc HMPAO-brain SPECT performed seven days after the last seizure showed a vast area of parieto-occipital hyperperfusion in the left hemisphere. Aggressive antiepileptic therapy dramatically improved the clinical symptoms and scintigraphic images, which corroborated the diagnosis of ictal paresis. This case highlights the role of SPECT in the evaluation of Sturge-Weber syndrome, not only to investigate progressive neurological deterioration, but also exacerbation of seizures or prolonged neurological deficits. In fact, it may be possible to document ongoing epileptic activity using SPECT, despite a non-contributory EEG, which may be of help in adapting a therapeutic strategy.

Misleading features of neuroimaging and electroencephalography: insulinoma misdiagnosed as temporal lobe epilepsy.

Epilepsy is a common disorder but diagnosis remains largely clinical. Although MRI and EEG significantly aid the diagnosis of epilepsy, these techniques may also be misleading and indicate abnormalities not related to phenomenology. Consequences of erroneous diagnosis of epilepsy may lead to aggressive and escalating pharmacotherapy with potentially serious side effects. Metabolic disorders, which may mimic epilepsy, should always be considered as they are potentially curable and may be fatal if untreated. We report a case of an insulinoma, misdiagnosed as temporal lobe epilepsy. We highlight the risks associated with misinterpretation of neuroimaging and EEG and outline an approach to differentiate between symptoms of insulinoma or neuroglycopenia and temporal epileptic seizures.