Limbic Encephalitis Research Articles

N°303 – Autoimmune limbic encephalitis with anti GAD-65 antibodies sucessfully treated with mycophenolate mofetil

N°303 – Autoimmune limbic encephalitis with anti GAD-65 antibodies sucessfully treated with mycophenolate mofetil

18F-FDG PET and MRI Evaluation of Paraneoplastic Limbic Encephalitis.

Autoimmune limbic encephalitis (paraneoplastic or nonparaneoplastic) is a rare condition involving autoantibodies against intracellular or cell-surface proteins of neurons. Patients typically present with acute and progressive neuropsychiatric symptoms. Although the criterion standard for diagnosis remains detection of autoantibodies in cerebrospinal fluid, there are characteristic imaging features that can aid in diagnosis, notably abnormalities in the bilateral medial temporal lobes on imaging, particularly with nuclear imaging. Here, we present 18F-FDG PET findings of paraneoplastic limbic encephalitis in a 65-year-old man.

Anti-LGI1 encephalitis with initiating symptom of seizures in children.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Case 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.

Neurosyphilis Presenting as Limbic Encephalitis: a Case Report (P10-10.007)

<h3>Objective:</h3> To present an interesting case of neurosyphilis mimicking limbic encephalitis. <h3>Background:</h3> Neurosyphilis can occur at any stage of infection and it classically presents as meningitis, cranial neuropathies, vasculitis, tabes dorsalis, or neuropsychiatric manifestations, however rarely temporal lobe abnormalities resembling limbic encephalitis have been reported. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 51-year-old male with no past medical history presents initially with 3 weeks of altered mental status, confusion and memory loss. Prior to admission to the hospital, he presented with a generalized tonic-clonic seizure. His MRI showed T2 hyperintensities in the left hippocampus, amygdala, and mesial temporal lobe with associated diffusion restriction. Cerebrospinal fluid (CSF) studies showed 58 white blood cells/mm3 (73% lymphocytes), a protein concentration of 165 mg/dL and a glucose concentration of 35 mg/dL. HIV serology, serum cryptococcal Antigen, HSV and VZV PCR on CSF and neuronal autoantibodies on serum were negative. EEG showed left lateralized periodic discharges. The patient was initially treated with empiric anti-infective therapy including acyclovir, ceftriaxone, and ampicillin. Subsequently, serum syphilis screen was positive with reflex Rapid Plasma Reagin (RPR) titer at 1:64. CSF Venereal Disease Research Laboratory (VDRL) was positive at 1:64. In light of these results, the patient was transitioned to intravenous aqueous penicillin G 24 million units daily through continuous infusion. His mental status markedly improved after a few days of treatment. Repeat EEG showed only mild encephalopathy. He was discharged on levetiracetam and high dose IV penicillin G to complete a 14-day course. <h3>Conclusions:</h3> Syphilis is commonly known as a great imitator; it is a treatable condition so it should not be missed. We need to be more cognizant of this diagnosis when evaluating patients with temporal lobe involvement on MRI, lymphocytic pleocytosis and hypoglycorrhachia. Although HSV and autoimmune diseases are the most common causes of limbic encephalitis, as presented in our case, syphilis testing should be considered. <b>Disclosure:</b> Dr. Hu has nothing to disclose. Dr. El Helou has nothing to disclose. Nayrobi Pena Cotui has nothing to disclose. Dr. Balobaid has nothing to disclose. Dr. Montalvo Perero has nothing to disclose.

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Autoimmune Encephalitis Criteria in Clinical Practice.

To assess the clinical practice applicability of autoimmune encephalitis (AE) criteria (2016). Medical records of 538 adults diagnosed with AE or related autoimmune encephalopathy at Mayo Clinic (not including pure movement disorders) were reviewed and AE guideline criteria applied. Of 538 patients, 288 were male (52%). The median symptom onset age was 55 years (range, 11-97 years; 16 had onset as children). All had other non-AE diagnoses reasonably excluded. Of 538 patients, 361 (67%) met at least possible criteria, having all 3 of subacute onset; memory deficits, altered mental status or psychiatric symptoms, and ≥1 supportive feature (new focal objective CNS finding, N = 285; new-onset seizures, N = 283; supportive MRI findings, N = 251; or CSF pleocytosis, N = 160). Of 361 patients, AE subgroups were as follows: definite AE (N = 221, 61%, [87% AE-specific IgG positive]), probable seronegative AE (N = 18, 5%), Hashimoto encephalopathy (N = 20, 6%), or possible AE not otherwise categorizable (N = 102, 28%). The 221 patients with definite AE had limbic encephalitis (N = 127, 57%), anti-NMDA-R encephalitis (N = 32, 15%), ADEM (N = 8, 4%), or other AE-specific IgG defined (N = 54, 24%). The 3 most common definite AE-IgGs detected were as follows: LGI1 (76, 34%), NMDA-R (32, 16%), and high-titer GAD65 (23, 12%). The remaining 177 patients (33%) not meeting possible AE criteria had the following: seizures only (65, 12% of all 538 patients), brainstem encephalitis without supratentorial findings (55, 10%; none had Bickerstaff encephalitis), or other (57, 11%). Those 57 "others" lacked sufficient supportive clinical, radiologic, or CSF findings (N = 26), had insidious or initially episodic onset of otherwise typical disorders (N = 21), or had atypical syndromes without clearcut memory deficits, altered mental status, or psychiatric symptoms (N = 10). Fifteen of 57 were AE-specific IgG positive (26%). Among the remaining 42, evidence of other organ-specific autoimmunity (mostly thyroid) was encountered in 31 (74%, ≥1 coexisting autoimmune disease [21, 50%] or ≥1 non-AE-specific antibodies detected [23, 53%]), and all but 1 had an objective immunotherapy response (97%). The 2016 AE guidelines permit autoimmune causation assessment in subacute encephalopathy and are highly specific. Inclusion could be improved by incorporating AE-IgG-positive patients with isolated seizures or brainstem disorders. Some patients with atypical presentations but with findings supportive of autoimmunity may be immune therapy responsive.

MOG antibody-associated encephalitis in adult: clinical phenotypes and outcomes (P13-5.020)

<h3>Objective:</h3> We investigated the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis (MOGAE) in adult patients. <h3>Background:</h3> Although MOG antibody-associated disease (MOGAD) can be associated with autoimmune encephalitis, the clinical features and outcomes of MOGAE in adults are largely unknown. <h3>Design/Methods:</h3> From an institutional cohort, we analyzed adult patients with MOGAE followed-up for more than one year. Disease severity was assessed using the modified Rankin scale (mRS) and Clinical Assessment Scales in Autoimmune Encephalitis (CASE) scores. Immunotherapy profiles, outcomes, and disease relapses were evaluated along with serial brain MRI data. <h3>Results:</h3> A total of 40 patients were enrolled and categorized into cortical encephalitis (18 patients), limbic encephalitis (LE, 5 patients), and acute disseminated encephalomyelitis (ADEM, 17 patients). 80.0% of patients achieved good clinical outcomes (mRS 0–2) and 40.0% relapsed. The LE subtype was associated with an older onset age (<i>P</i>=0.004) and poor clinical outcomes (<i>P</i>=0.014) than the other subtypes but with a low rate of relapse (0.0%). 21/25 (84.0%) relapse attacks were associated with an absence or short (≤6 months) immunotherapy maintenance. On MRI, the development of either diffuse cerebral or medial temporal atrophy within the first six-month was correlated with poor outcomes. MOG-antibody was co-present with anti-N-methyl-D-aspartate receptor (NMDAR)-antibody in 13 patients, in whom atypical clinical presentation (cortical encephalitis or ADEM, <i>P&lt;</i>0.001) and disease relapse (46.2% vs. 0.0%, <i>P&lt;</i>0.001) were more frequent compared to conventional NMDAR encephalitis without MOG-Ab. <h3>Conclusions:</h3> Outcomes are different according to the three phenotypes in MOGAE. Short immunotherapy maintenance is associated with relapse, and brain atrophy was associated with poor outcomes. Patients with dual antibodies of NMDAR and MOG have a high relapse rate. <b>Disclosure:</b> Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biofire Diagnostics. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GC pharma. The institution of Prof. Lee has received research support from GC pharma. Prof. Kim has received intellectual property interests from a discovery or technology relating to health care. Prof. Chu has nothing to disclose. Prof. Lee has nothing to disclose. Woo-jin Lee has nothing to disclose.

Candida dubliniensis Meningitis in Immunocompetent Adults - case report and review of literature (P10-10.001)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> We report a case and review the cases of <i>Candida dubliniensis</i> meningitis in immunocompetent adults. <h3>Results:</h3> 32 years old man with history of intravenous drug use (IVDU) presented with seizures, nuchal rigidity, and papilledema. Head CT showed communicating hydrocephalus and brain and spine MR showed diffuse leptomeningeal enhancement extending to the cauda equina. HIV, syphilis, and quantiferon-gold tests were negative but his CD4 count was 203 (430 – 1185/mm3). Lumbar puncture showed opening pressure of 45 mm H2O, CSF protein &gt; 392 mg/dl (15–45), glucose 5 mg/dL (40–70), nucleated cells 246 (0–5), 83% lymphocytes, red blood cells 1 (0–1). CSF meningitis panel was negative, but encephalitis panel showed NMDA receptor antibody. 1,3-Beta-D-glucan was 79 (&lt;60 pg/mL) in the serum and 295 in the CSF and CSF cultures grew <i>Candida dublinens</i>is. <h3>Conclusions:</h3> Chronic base of the skull meningitis has many causes including inflammatory conditions, malignancies, and infections. Invasive <i>C. dublinensis</i> infection is very rare and usually associated with immunodeficiency (HIV or post-transplant). This is the fourth case of <i>C. dublinensis</i> in an immunocompetent host described in the literature. Like our case, in two of those three reports the infection was associated with IVDU, and this information is not available for the third case. This corroborates the hypothesis that IVDU could be a risk factor for this infection. Regarding his CSF NMDA receptor antibody, he did not have limbic encephalitis, dysautonomia, seizures or psychiatric symptoms. There is a known association of this antibody and ovarian teratomas and herpes simplex encephalitis but no association with <i>Candida sp.</i> is known. Despite his low CD4 count he did not have other opportunistic infections. No etiology was identified for this finding. <b>Disclosure:</b> Dr. Horta has nothing to disclose. Dr. White has nothing to disclose. Dr. Greige has nothing to disclose. Dr. Askari has nothing to disclose. Dr. Cervantes-Arslanian has nothing to disclose.

Caspr2 Antibody-Mediated Ataxia, Parkinsonism, and Epilepsy: A Case for Escalating Immunotherapy. (P13-11.007)

<h3>Objective:</h3> To report a rare presentation of anti-Caspr2 syndrome treated successfully with rituximab. <h3>Background:</h3> Anti-Caspr2 syndrome has a variety of clinical phenotypes including encephalopathy, seizure, psychiatric disturbances, respiratory failure, dysautonomia, peripheral nerve dysfunction, as well as ataxia of a constant or episodic nature.¹ In many of the cases with ataxia, there is associated limbic encephalitis.² Anti-Caspr2 syndrome with ataxia, parkinsonism and seizure has only been reported once in the literature.³ This symptomatology can be easily mistaken for an atypical parkinsonism like cerebellar multiple systems atrophy, or spinocerebellar ataxia type 2 but this treatable cause is an important consideration. <h3>Design/Methods:</h3> To report a case of anti-Caspr2 syndrome presenting with pure ataxia, then progressing to parkinsonism, and epilepsy; its successful treatment; and accompanying video examinations. <h3>Results:</h3> A 71 year-old man was referred for 8 months of progressive, generalized ataxia and dysarthria. Immune-mediated ataxia was considered given the subacute course with rapid progression. He was found to have a Caspr2 antibody titer of 1:100. Evaluation for malignancy was unremarkable. Lumbar puncture revealed Caspr2 antibody positivity. The patient was treated with 4 days of intravenous steroids and immunoglobulins with significant improvement. He relapsed four months later with lower extremity weakness and ataxia. Despite maintenance intravenous immunoglobulin, his ataxia continued to progress. He then developed focal seizures with impaired awareness and left sided parkinsonism. He was started on rituximab immunotherapy for ongoing disease activity. His ataxia and parkinsonism significantly improved to near-baseline with continued stability 6 months later. <h3>Conclusions:</h3> This case illustrates an example of an autoimmune-mediated cerebellar ataxia of subacute onset with progression to parkinsonism and epilepsy. Special consideration for anti-Caspr2 syndrome should be taken in cases of progressive ataxia with accompanying neurologic features of parkinsonism and seizure. Escalation to rituximab can be considered for patients who continue to progress despite preliminary immunotherapy. <b>Disclosure:</b> Dr. Sugar has nothing to disclose. Dr. Witek has nothing to disclose.

Acute Fulminant Encephalitis in the Setting of Acute COVID-19 Infection (P12-3.008)

<h3>Objective:</h3> NA <h3>Background:</h3> Encephalitis in the setting of COVID-19 has been reported, however the mechanism by which SARS-CoV-2 causes encephalitis remains unclear. We aimed to describe a case of fulminant limbic encephalitis associated with acute COVID-19 infection. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 33-year-old COVID-19 positive female presented after being found unresponsive with seizure-like activity. On arrival, patient was comatose with intermittent left gaze deviation, weak gag and cough reflexes, and no movement to pain. She was intubated for airway protection (without hypoxia). Continuous EEG demonstrated generalized and bilaterally independent epileptiform discharges, with no electrographic or clinical seizures. Patient was prophylactically started on levetiracetam. Brain MRI revealed scattered DWI and T2 hyperintensities involving supratentorial and infratentorial areas more prominent in temporal lobes. CSF analysis showed mild neutrophilic pleocytosis; protein and glucose were normal. Infectious, autoimmune, and paraneoplastic encephalopathy in CSF/serum panels were negative. CSF COVID-19 PCR was negative. ESR, CRP and ferritin were mildly elevated. High-dose steroids and intravenous immunoglobulin were initiated. After 7 days repeated brain MRI demonstrated progression of T2 hyperintensities including midbrain, cerebral peduncles, and right hemispheric cortical ribboning. Patient continued to decline with gradual loss of brainstem reflexes and downward gaze deviation with ocular bobbing movements. Due to clinical deterioration the patient was transitioned to comfort care and deceased after extubating. <h3>Conclusions:</h3> There have been increasing reports of severe encephalitis subtypes among younger COVID-19 patients commonly associated with poor outcomes compared to other subtypes of encephalitis. To our knowledge this is the first case of encephalitis associated with COVID-19 infection with no response to immunomodulatory therapies. Other possible etiologies in this case include hypoxic injury, hypoglycemia, or toxic insults, which were considered less likely given clinical scenario. In our case, PCR of CSF was negative for COVID-19 which raises possibility of secondary hyperinflammation or molecular mimicry as potential causes. <b>Disclosure:</b> Dr. Kherallah has nothing to disclose. Dr. Manrique has nothing to disclose. Dr. Vennavaram has nothing to disclose. Dr. Samaha has nothing to disclose.

Neuropsychiatric symptoms of autoimmune limbic encephalitis, between neurology and psychiatry

Neuropsychiatric symptoms of autoimmune limbic encephalitis, between neurology and psychiatry

Seizure semiology and predictors of outcomes in Chinese patients with glutamic acid decarboxylase antibody-associated neurological syndrome

BackgroundIn the current study, seizure semiology and potential predictive factors of seizure outcomes in glutamic acid decarboxylase antibody (GAD Ab)-associated neurological syndrome were investigated.MethodsIn this study, 32 Chinese patients with GAD Ab-associated neurological syndrome who presented with seizures at Peking Union Medical College Hospital from January 2017 to October 2022 were reviewed; 30 had a follow-up duration of more than 1 year.ResultsAmong the 32 patients, 10 presented with epilepsy alone. Concomitant neurological syndromes were observed in 22 patients, including limbic encephalitis (n = 20), stiff-person syndrome (SPS, n = 1), and cerebellar ataxia (n = 1). Bilateral tonic–clonic seizures were observed in 21 patients (65.6%). Focal seizures occurred in 27 patients (84.4%); 17 had focal motor seizures and 18 focal non-motor seizures. Among 30 patients with long-term follow-up, 11 (36.7%) were seizure-free. Acute/subacute onset (p = 0.049) and comorbidity of limbic encephalitis with epilepsy (p = 0.023) led to better seizure outcomes. Patients with persistent epilepsy were more likely to have focal seizure (p = 0.003) and higher frequency of seizure (p = 0.001). Furthermore, these patients tended to have longer intervals from onset to immunomodulatory treatments. Early immunotherapy (within 6 months from onset) was administered in 81.8% of seizure-free patients but only in 42.1% of patients with persistent seizures. However, steroid and immunosuppressant duration did not differ in the two groups. Repeated serum GAD Ab tests during the follow-up showed no association with seizure outcomes.ConclusionsThe seizure manifestations are diverse and variable. Approximately one third of patients achieved seizure remission during long-term follow-up. The type and frequency of seizures may influence the seizure outcomes. Early immunotherapy, especially within 6 months, may lead to better seizure outcomes.

Comparative Effects of Domain-Specific Human Monoclonal Antibodies Against LGI1 on Neuronal Excitability.

Autoantibodies to leucine-rich glioma inactivated protein 1 (LGI1) cause an autoimmune limbic encephalitis with frequent focal seizures and anterograde memory dysfunction. LGI1 is a neuronal secreted linker protein with 2 functional domains: the leucine-rich repeat (LRR) and epitempin (EPTP) regions. LGI1 autoantibodies are known to interfere with presynaptic function and neuronal excitability; however, their epitope-specific mechanisms are incompletely understood. We used patient-derived monoclonal autoantibodies (mAbs), which target either LRR or EPTP domains of LGI1 to investigate long-term antibody-induced alteration of neuronal function. LRR- and EPTP-specific effects were evaluated by patch-clamp recordings in cultured hippocampal neurons and compared with biophysical neuron modeling. Kv1.1 channel clustering at the axon initial segment (AIS) was quantified by immunocytochemistry and structured illumination microscopy techniques. Both EPTP and LRR domain-specific mAbs decreased the latency of first somatic action potential firing. However, only the LRR-specific mAbs increased the number of action potential firing together with enhanced initial instantaneous frequency and promoted spike-frequency adaptation, which were less pronounced after the EPTP mAb. This also led to an effective reduction in the slope of ramp-like depolarization in the subthreshold response, suggesting Kv1 channel dysfunction. A biophysical model of a hippocampal neuron corroborated experimental results and suggests that an isolated reduction of the conductance of Kv1-mediated K+ currents largely accounts for the antibody-induced alterations in the initial firing phase and spike-frequency adaptation. Furthermore, Kv1.1 channel density was spatially redistributed from the distal toward the proximal site of AIS under LRR mAb treatment and, to a lesser extant, under EPTP mAb. These findings indicate an epitope-specific pathophysiology of LGI1 autoantibodies. The pronounced neuronal hyperexcitability and SFA together with dropped slope of ramp-like depolarization after LRR-targeted interference suggest disruption of LGI1-dependent clustering of K+ channel complexes. Moreover, considering the effective triggering of action potentials at the distal AIS, the altered spatial distribution of Kv1.1 channel density may contribute to these effects through impairing neuronal control of action potential initiation and synaptic integration.

Anti-amphiphysin encephalitis: Expanding the clinical spectrum.

An analysis of the clinical features of autoimmune encephalitis accompanied by anti-amphiphysin antibodies. The data of encephalitis patients with anti-amphiphysin antibodies were retrospectively evaluated, including demographics, neurological and laboratory findings, imaging, treatment, and prognostic predictions. Ten patients aged between 29 and 78 years (median age 52 years) were included. The male: female ratio was 4:6. Limbic encephalitis was found in nine patients while epileptic seizures were present in seven patients. All patients showed anti-amphiphysin antibody positivity in sera while one ninth was positive for CSF antibody. The EEG findings were abnormal, including reductions in background activity, and the presence of diffuse slow waves, sharp waves, and spikes and waves. Five patients showed signs of increased T2 signals in the medial temporal lobe on MRI while PET showed either hyper- or hypo-metabolic changes in several brain regions, including the temporal lobe, hippocampus, basal ganglia, frontal and parietal cortices. Nine of ten patients were treated with immunotherapy, with improvements of varying degrees. There was a significant reduction in seizure frequency, and all patients were seizure-free at last follow-up. Autoimmune encephalitis with anti-amphiphysin antibodies has a variety of clinical manifestations. The most common symptom is limbic encephalitis. Although relief from seizures can be achieved relatively easily, many patients suffer psychiatric, cognitive, and sleep sequelae. The disease was found to be associated with a lower incidence of cancer than has been previously reported for paraneoplastic neurologic syndromes.

Anti-LGI1 encephalitis: A family affair

Here we describe the second ever-reported case of familial anti-leucine-rich glioma-inactivated protein 1 (LGI1) limbic encephalitis (LE). Two elderly Caucasian sisters presented with psychiatric symptoms and cognitive impairment, followed by faciobrachial dystonic seizures. Anti-LGI1 antibodies were detected in their serum. Considering they had been living in distant regions for decades, environmental factors could be ruled out. Human leukocyte antigen (HLA) genotyping revealed that both carried HLA-DRB1*07, found in 90% of anti-LGI1 encephalitis patients, HLA-DQA1*02:01 and HLA-DQB1*03:03, commonly associated with DRB1*07:01. Considering the exceptional nature of familial cases, as-yet-unknown genetic contributors other than HLA might play a role in our siblings.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes.

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.

Ophelia syndrome as single association: neoplastic limbic encephalitis and Hodgkin lymphoma

Ophelia syndrome as single association: neoplastic limbic encephalitis and Hodgkin lymphoma

Clinical features of 28 cases of anti-leucine-rich glioma-inactivated protein 1 encephalitis and anti-contactin-associated protein-like 2 encephalitis.

Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis. Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared. In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed T2WI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all P<0.05). Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.

Metabolic phenotyping of pilomotor seizures in autoimmune encephalitis.

Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP are still unclear. To have a better understanding of IP underlying mechanisms, the current study investigated whole-brain metabolic networks for the analysis of AE-associated IP. Patients with AE and IP diagnosed at our Institute between 2018 and 2022 were selected. We then investigated the brain regions associated with AE-associated IP using positron emission tomography (PET). Anatomometabolic changes (interictal 18 F fluorodeoxyglucose PET) in AE patients with IP were compared with those of AE patients of similar age without IP (p-voxel <0.001, uncorrected). Sixteen patients showed significant IP. The overall IP prevalence was 4.09% of patients with AE and 12.9% of patients with limbic encephalitis. The most common autoantibodies were against LGI1 (68.8%) followed by GAD65 (6.3%), NMDA (6.3%), GABAb (6.3%), CASPR2 (6.3%), and antibodies recognizing both GAD65 and mGLUR5 (6.3%). Most patients responded well to immunotherapy. Analysis of the imaging results at the voxel level showed that patients with IP had hypermetabolic changes in the right inferior temporal gyrus, suggesting involvement of this brain region in IP. Our findings indicate that IP as an uncommon AE-associated manifestations should be recognized. We observed that the metabolic pattern of IP was conspicuous in the right inferior temporal gyrus.

Paraneoplastic Kelch-like protein 11 antibody-associated cerebellar and limbic encephalitis caused by metastatic “burned-out” seminoma – A scar(r)y phenomenon

IntroductionThe diagnosis of paraneoplastic neurologic syndromes is challenging when the primary tumor masquerades as scar tissue (i.e. “burned-out”). MethodsCase report. ResultsA 45-year-old male patient presented with progressive cerebellar symptoms and hearing loss. Initial screening for malignancy and extensive testing of paraneoplastic and autoimmune neuronal antibodies gave negative results. Repeated whole-body FDG-PET CT revealed a single paraaortic lymphadenopathy, metastasis of a regressed testicular seminoma. Anti-Kelch-like protein-11 (KLHL11) encephalitis was finally diagnosed. ConclusionOur case highlights the importance of continued efforts to find an often burned-out testicular cancer in patients with a highly unique clinical presentation of KLHL11 encephalitis.