Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease
PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.
Rare autoimmune encephalitis presenting as fluid-attenuated inversion recovery-hyperintense lesions in anti-Myelin oligodendrocyte glycoprotein-associated encephalitis and seizures accompanied with anti-IgLON5 antibody
The symptoms of Anti-IgLON5 antibody-related encephalopathy are heterogeneous. The most prominent characteristic is sleep dysfunction (REM and non-REM sleep parasomnia), obstructive sleep apnea syndrome, gait instability, and bulbar dysfunction. Sleep disturbance is a prominent clinical manifestation of anti-IgLON5 antibody encephalopathy. However, this case only showed an absence of the REM phase, and no obvious sleep disturbance was observed. This case did not show extrapyramidal symptoms that are characteristic of IgLON5 antibody encephalopathy. This may be related to the short onset time of the patient, because some reports show that IglON5 has a slow onset and a longer course of disease.
AMPA Receptor Encephalitis in a Patient With Metastatic Breast Cancer Receiving Palbociclib: A Case Report
Results: A 55-year-old woman with metastatic breast cancer presented with new-onset neurologic symptoms. After diagnosis and treatment in 2008, she was in remission from 2010 to 2021. In April 2021, she developed metastatic recurrence. She started palbociclib in June 2021. PET scan in August 2021 showed improved metastases without new lesions. In September 2021, she developed encephalopathy, vertical nystagmus, and ataxia. Workup revealed AMPA-R antibodies. Palbociclib was stopped, and she received steroids, IVIg, and rituximab with marked improvement in her neurologic symptoms.
Structural mechanisms of GABA A receptor autoimmune encephalitis
Epileptic Seizures and Right-Sided Hippocampal Swelling as Presenting Symptoms of Anti-IgLON5 Disease: A Case Report and Systematic Review of the Literature
We identified 161 cases from 65 publications. With heterogeneous clinical manifestations, we found that bulbar dysfunction, sleep apnea, gait instability and neurocognitive and behavioral symptoms are the most common symptoms of anti-IgLON5 disease. Anti-IgLON5 antibodies presented a higher positive rate and titer in the serum than in the cerebrospinal fluid (CSF). Haplotype DRB1*10:01-DQB1*05:01 is highly correlated with anti-IgLON5 disease. Only 38 patients have presented distinctive MRI alterations (26.2%). Approximately half of the cases are responsive to immunosuppressive or immunomodulatory treatment.
Anti-IgLON5 disease is characterized by various clinical manifestations and laboratory findings. Immunotherapy may be effective in treating anti-IgLON5 disease, but the results are far from satisfactory. Studies with larger sample sizes are required to improve the current understanding of this disorder.
A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study
IgLON5 antibodies identify a unique non-REM and REM parasomnia with sleep breathing dysfunction and pathological features suggesting a tauopathy.
Anti-IgLON5 Disease – The Current State of Knowledge and Further Perspectives
The aim of this review is to summarize the current knowledge concerning anti-IgLON5 disease; mechanisms underlying its cause, symptomatology, clinical progression, differential diagnosis and treatment, which could be helpful in clinical practice and future research.
Identification of Anti-Collapsin Response Mediator Protein 2 Antibodies in Patients With Encephalitis or Encephalomyelitis
New Antibody in AE identified. anti-CRMP2 Ab An increasing number of autoimmune encephalitis (AE)-associated autoantibodies have been successfully characterized. However, many cases of AE remain unexplained on account of unknown antibodies. Two patients have been identified with this antibody With Encephalitis or Encephalomyelitis. Both responded well to immunotherapy with no residual neoplasm (benign mass/tumor in this case). This is an extracellular antibody (ab), which means it attaches to the outside of the healthy cell it is attacking). Extracellular antibodies are common in AE and highly responsive to immunotherapy because they are exposed out in the open so the treatment can effect them easily.
Anti-Neuronal Nuclear Antibody 3 Autoimmunity Targets Dachshund Homolog 1
In this study we identified dachshund-homolog 1 (DACH1), a tumor suppressor protein, as the antigenic target of ANNA3-IgG. Neurologic manifestations were diverse and while a homogeneous neurologic phenotype was lacking, 90% had evidence of a malignancy, the majority being of neuroendocrine lineage.
Clinico-radiological characteristics of anti-myelin oligodendrocyte glycoprotein antibody-associated autoimmune encephalitis in children
Anti-MOG antibody-associated encephalitis accounts for a significant proportion of clinically defined paediatric patients with autoimmune encephalitis. Anti-MOG antibody-associated encephalitis should be included in the clinical spectrum of anti-MOG-associated diseases.
Autoimmune basal ganglia encephalitis associated with anti-recoverin antibodies: A case report
Clinicians should be aware of the possibility of autoimmune basal ganglia encephalitis showing anti-recoverin Abs without CAR syndrome or malignancy and should consider administering HD-IVIG therapy.
Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy Presenting as Mild Encephalopathy with Reversible Splenium Lesion
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is scarce and usually presents as meningoencephalomyelitis. Here, we offer the case of an atypical presentation of GFAP-astrocytopathy. First reported association between MERS and GFAP astrocytopathy in an adult patient. Clinical presentation of GFAP astrocytopathy usually includes various neurologic symptoms and can lead to misdiagnosis.
Autoimmune Brainstem Encephalitis: An Illustrative Case and a Review of the Literature
Autoimmune BSE is only one of many causes of BS dysfunction. For instance, various disease states may also target the BS and should be included in the differential diagnoses of BSE. These include but are not limited to osmotic demyelination syndrome commonly in the context of hyponatremia, hypertensive encephalopathy in patients presenting with severe hypertension, visual symptoms and seizures, and Wernicke encephalopathy in patients with thiamine deficiency and opthalmoparesis. Furthermore, the presence of fever in an immunocompromised state should always raise the suspicion of an underlying infectious cause. While infectious and autoimmune etiologies are more likely seen in young patients, neoplastic diseases are more prevalent in older populations. Given this wide array of causes of BS dysfunction, awareness of the multiple disorders that may manifest with BS lesions and a comprehensive approach to diagnosis are essential for proper management. The importance of early recognition of autoimmune BSE cannot be overemphasized since the damage is often reversible with appropriate therapy. Long-term management is dependent on the precise underlying etiology. Although some entities follow a monophasic course, others are prone to relapses. Early institution of immunotherapy after the acute stage can have a significant impact on the likelihood of recurrent inflammatory events and the long-term prognosis.
Encephalitis with autoantibodies against the glutamate kainate receptors GluK2
New antibody identified. GluK2-abs associate with an encephalitis with prominent clinico-radiological cerebellar involvement. The antibody effects are predominantly mediated by internalization of GluK2.
Six of 8 patients developed acute encephalitis and clinical or MRI features of predominant cerebellar involvement (4 presenting as cerebellitis which in 2 caused obstructive hydrocephalus), and 2 had other syndromes (1 with cerebellar symptoms). One of the samples showed mild reactivity with non-kainate receptors (AMPAR and NMDAR) leading to identify 6 additional cases with GluK2-abs among patients with anti-AMPAR (5/71) or anti-NMDAR encephalitis (1/73). GluK2-abs internalized GluK2 in HEK293 cells and neurons; these antibody-effects were reversible in neurons.
Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report
To the best of our knowledge, this is the first report of the possible coexistence of MOGAD and anti-Caspr2 antibody-associated autoimmune encephalitis.
Anti-Ma encephalitis masquerading as Wernicke encephalopathy
Anti-Ma encephalitis is a disease usually associated with testicular cancer in young male patients. Anti-Ma encephalitis presented as Wernicke encephalopathy-like symptoms and with gastric cancer is rare. Here, we report a case of anti-Ma encephalitis with gastric cancer in an elderly patient, which has been misdiagnosed of Wernicke encephalopathy.
Chorea in IgLON5‐Mediated Autoimmune Encephalitis
IgLON5‐associated autoimmunity was first described as a central nervous system disorder with prominent sleep disturbances. Since the initial description, case series of this autoimmune encephalopathy have also reported various movement disorders. Here we describe a case of IgLON5‐associated autoimmune disease manifesting subacute progressive chorea, intermittent bulbar dysfunction, and sleep disorders.
Brain paraneoplastic syndromes in a patient with mediastinal ganglioneuroma
In conclusion, PNS should be considered in the differential diagnosis of patients with neurological syndromes with or without onconeural antibodies, and they may appear several months or even years before the detection of the underlying tumor.
Antibodies to the α3 subunit of the ganglionic-type nicotinic acetylcholine receptors in patients with autoimmune encephalitis
Autonomic symptoms are frequently observed in autoimmune encephalitis.
We assessed the clinical features and gAChRα3 antibodies in patients with autoimmune encephalitis.
Cardiovascular autonomic symptoms were found to be common in autoimmune encephalitis.
We detected gAChRα3 antibodies in about 30% of patients with autoimmune encephalitis.
High-resolution epitope mapping of anti-Hu and anti-Yo autoimmunity by programmable phage display
The results presented here further demonstrate the utility and high-resolution capability of phage immunoprecipitation sequencing for both basic science and clinical applications and for better understanding the antigenic targets and triggers of paraneoplastic neurological disorders.
Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis
Anti-Dopamine Receptor 2 Antibody-Positive Encephalitis in Adolescent
Clinical Characteristics of Anti-GABA-B Receptor Encephalitis
Anti-gamma-aminobutyric acid receptor type A encephalitis a review
Clinical and imaging features of children with autoimmune encephalitis and MOG antibodies
AE associated with serum MOG abs represents a distinct form of autoantibody-mediated encephalitis in children. We therefore recommend including MOG abs testing in the workup of children with suspected AE.
Mild Encephalitis/Encephalopathy with reversible splenial lesion syndrome: An unusual presentation of anti-GFAP astrocytopathy
Anti-GFAP astrocytopathy is a rare condition in adults and children and specific MRI lesions have been suggested.
Clinical outcome is good in most of the cases after immunotherapies.
The pathogenicity of anti-GFAP antibodies is far from being demonstrated.
Anti-GFAP antibodies should be tested for meningo-encephalitis with normal or MERS suggestive MRI, as treatment may differ.
Encephalitis with radial perivascular emphasis: Not necessarily associated with GFAP antibodies
Autoimmune Encephalitis and CSF Anti-GluR3 Antibodies in an MS Patient after Alemtuzumab Treatment
Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis
GABAA receptor autoimmunity
LGI1 antibodies alter Kv1.1 and AMPA receptors
Glial fibrillary acidic protein IgG related myelitis: characterisation and comparison with aquaporin-4-IgG myelitis
Beyond the limbic system: disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis
Auto-antibodies against P/Q- and N-type voltage-dependent calcium channels mimicking frontotemporal dementia
Study in Lancet 9% of 228 patients tested positive for antibodies in AE with 1st time Psychosis
Patients with MOG antibody were more likely to have seizures than patients with AQP4-IgG
Autoimmune encephalitis with GABAA receptor antibodies in a 10-year-old girl: case study
Antibody-associated CNS syndromes without signs of inflammation in the elderly
CNS syndromes associated with antibodies against metabotropic receptors
Autoantibody-mediated diseases of the CNS: Structure, dysfunction and therapy
Paraneoplastic limbic encephalitis in a patient with extensive disease small-cell lung cancer.
Prevalence & clinical characteristics of serum neuronal cell surface antibodies in 1st-episode psychosis
Neurexin-3 : A new antibody target in autoimmune encephalitis
Autoantibodies in Neuropsychiatric Disorders
Clinical and imaging characteristics of 16 patients with autoimmune neuronal synaptic encephalitis
Abstract: Antibodies to GABAA receptor α1 and γ2 subunits: clinical and serologic characterization
FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types
Paraneoplastic and Other Autoimmune Disorders of the Central Nervous System
Neuropsychiatric AE w/out VGKC-complex, NMDAR, and GAD
A. Vincent: Autoantibodies to neuronal surface antigens in thyroid antibody-positive and -negative limbic encephalitis
Seronegative acute encephalitis following COVID-19 vaccines: a case series of an overlooked diagnosis with literature review
We report a case series of three clinical pictures consistent with the diagnosis of AIE triggered by COVID-19 vaccines. In all three cases, criteria for possible AIE defined by Graus et al. were fulfilled.
Anti-mGluR1 encephalitis: Case illustration and systematic review
Anti-mGluR1 encephalitis manifests as symptoms of cerebellar pathology. Although the natural history has not been completely elucidated, early diagnosis with prompt initiation of immunotherapy could be imperative. Any patient suspected to have autoimmune cerebellitis should be tested for the presence of anti-mGluR1 antibody in the serum and cerebrospinal fluid. Escalation to an aggressive therapy approach should be applied in cases that do not respond to first-line therapies, and extended follow-up durations are required in all cases.
Clinical, imaging features and outcomes of patients with anti-GFAP antibodies: a retrospective study
There was no statistically significant difference in clinical symptoms and imaging findings between children and adult patients with anti-GFAP antibodies; Patients with anti-GFAP antibodies may present with normal MRI findings or delayed MRI abnormalities, and patients with overlapping antibodies were common. Most patients had monophasic courses, and those with overlapping antibodies were more likely to relapse. Children were more likely than adults to have no disability. Finally, we hypothesize that the presence of anti-GFAP antibodies is a non-specific witness of inflammation.
Patient characteristics and outcome in patients with anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis
Four patients (44%) were males, and the median age at presentation was 54 years (range, 25-85). Short-term memory loss was the most common initial symptom. Additional types of autoantibodies were identified in three patients. After presentation, four patients were found to have tumors: two with small cell lung cancer, one with ovarian teratoma, and one with thymoma. All patients accepted first-line immune therapy, and follow-up was available from 8 patients (median 20 weeks, range 4-78). At the last follow-up, three patients showed good outcomes (modified Rankin scale [mRS] 0-2; 37.5%). Five patients showed poor outcomes (mRS 3-6; 62.5%): two had minimal changes and remained hospitalized, two had residual severe cognitive impairments, and one patient died during follow-up. Outcomes were worse among patients with tumors. Finally, only one patient experienced relapse during follow-up.
Septin-3 autoimmunity in patients with paraneoplastic cerebellar ataxia
Septin-3 is a novel autoantibody target in patients with paraneoplastic cerebellar syndromes. Based on our findings, RC-IIFA with HEK293 cells expressing the septin-3/5/6/7/11 complex may serve as a screening tool to investigate anti-septin autoantibodies in serological samples with a characteristic staining pattern on neuronal tissue sections. Autoantibodies against individual septins can then be confirmed by RC-IIFA expressing single septins.
EEG-Delta brushes in DPPX encephalitis – Welcome to the club
Extreme delta brushes are a phenomenon observed in 30 to 60% of all patients with anti-NMDAR encephalitis. The pattern was initially considered pathognomonic for anti-NMDAR encephalitis, but has been shown to occur rarely in other encephalitic syndromes as well Here, researchers report to their best knowledge the first case of anti-DPPX encephalitis-related extreme delta brush-EEG. Of note, the unusual EEG-pattern and the CSF-specific oligoclonal bands, as well as the positive APE score triggered the rapid serological testing for autoimmune encephalitis, which led to the correct diagnosis.
Frequency of New or Enlarging Lesions on MRI Outside of Clinical Attacks in Patients With MOG-Antibody–Associated Disease
105 patients were included. Discussion New or enlarging MRI lesions rarely develop outside of clinical attacks in MOGAD differing from MS. Surveillance MRIs in MOGAD have limited utility with implications for clinical practice and trial design.
MOG antibody-associated encephalitis in adult: clinical phenotypes and outcomes
A total of 40 patients were enrolled in study. Conclusions: 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.
A case of GFAP-IgG positivity followed by anti-NMDAR encephalitis
Anti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected.
Serological biomarkers in autoimmune GFAP astrocytopathy
The present study identified a series of serological proteins that were differentially expressed between GFAP-A patients and NMOSD patients compared to HCs and verified a profile of serological DEPs that was unique to GFAP-A patients. We described the correlations between serological protein levels and CSF anti-GFAP antibody titers and clinical severity. We found that CSF anti-GFAP antibody titers significantly negatively correlated with EG-VEGF, follistatin, insulin and NT-3. Clinical severity (mRS scores) significantly positively correlated with MIP-3a, PDGF-BB, HGF, GM-CSF and TARC. CSF GFAP IgG is essential for diagnosis, but it is not a suitable biomarker. The serological proteins characterized in this study may be useful biomarkers for GFAP-A.
Motor-neuron-disease-like phenotype associated with IgLON5 disease
Here we describe four cases of IgLON5 autoimmunity with motor neuron involvement and evaluate an additional 109 probable or definite amyotrophic lateral sclerosis cases seen in our neuromuscular clinic for IgLON5-IgG seropositivity. The presence of parasomnias, vocal cord dysfunction or hyperkinetic movements in a patient with motor-neuron-disease-like phenotype should prompt evaluation for IgLON5-IgG autoantibodies. Recognition and treatment of this autoimmune disease with immunosuppressive agents may bring about significant neurological improvement in a minority of cases.
Cerebellar Ataxia With Anti-DNER Antibodies Outcomes and Immunologic Features
DNER ataxia is a treatable condition in which nearly a third of patients have a favorable outcome. DNER antibodies bind to the surface of Purkinje cells and are therefore potentially pathogenic, supporting the use of B-cell–targeting treatments.
Anti-Ma2 paraneoplastic autoimmune encephalitis
Paraneoplastic syndromes are a heterogeneous group of conditions affecting cancer patients, where the symptoms are not owing to the local effects of the tumor but instead owing to humoral or immunologic effects. Paraneoplastic neurological syndromes (PNS) develop in less than 1% of cancer patients and can affect any part of the nervous system. A variety of PNS phenotypes are associated with anti-Ma2 antibody, primarily encephalitis with a predominant involvement of brainstem, limbic and diencephalic structures. We describe a case of anti-Ma2 autoimmune encephalitis with a recurrent course in a patient with two different primary tumors in the anamnesis.
Early and aggressive treatment may modify anti Hu associated encephalitis prognosis
Anti-Hu limbic encephalitis is a paraneoplastic syndrome in adults. In children, rare cases of anti-Hu limbic encephalitis were reported mostly without underlying tumors and clinical outcome are usually severe. Here, we describe a 4 year-old girl who developed cerebellar syndrome with abnormal behavior. The brain MRI showed several T2/FLAIR bilateral hyperintensities and auto-immune assessment showed positive anti-Hu antibodies. CT-scan revealed ganglioneuroblastoma which was surgically removed 3 months after onset. Aggressive immunotherapy including dexamethasone, rituximab and IV immunoglobulins were used and a marked neurological improvement soon after 9 months of onset was observed with a child who was able to go back to school. The short delay between diagnosis and start of aggressive immunotherapy demonstrate the paramount importance of early diagnosis and early specific therapy after onset of symptoms.
Seronegative autoimmune diseases: A challenging diagnosis
Seronegative- Autoimmune diseases (AID) pose a peculiar challenge for clinicians who must often rely on clinical and histopathological evidence for making a definitive diagnosis. Table 2 summarizes the available antibodies used for the diagnosis of AID, along with their limitations and factors leading to seronegativity. Although the accuracy of these antibodies has generally improved over time, yet some shortcomings limit their usefulness in clinical practice.
Immune and Genetic Signatures of Breast Carcinomas Triggering Anti-Yo–Associated Paraneoplastic Cerebellar Degeneration
This study indicates that there is a morphophenotypical signature of Yo-PCD BCs: invasive HER2-driven carcinoma overexpressing mutated CDR2L and metastasizing early to regional lymph nodes despite massive infiltration by effector immune cells with an overwhelming predominance of IgG-plasma cells. This specific BC profile, closely linked to HER2-driven carcinogenesis, undoubtedly participates in triggering the immune tolerance breakdown, leading to Yo-PCD autoimmunity.
Anti-homer-3 Antibody Encephalitis in a 10-Year-Old Child: Case Report and Review of the Literature
Anti-Homer-3 cerebellar ataxia with encephalopathy should be considered within the differential diagnosis of acute inflammatory cerebellar disease in children and it may coexist with VGCC antibodies.
Positive Predictive Value of MOG-IgG for Clinically Defined MOG-AD Within a Real-World Cohort
During the specified period for data analysis, serum MOG-IgG testing was performed in a total of 1,877 patients. Among the 67 true positive cases, prevalence of clinical phenotypes in order of frequency was: optic neuritis (62.7%, of which 27 cases were unilateral and 15 cases were bilateral), ADEM (14.9%), transverse myelitis (13.4%, of which 5 cases had longitudinally-extensive lesions and 4 cases had short segment lesions), concurrent optic neuritis and transverse myelitis (6%) and brainstem syndrome (3%). Using a MOG-IgG titer cut-off of ≥1:40, PPV, irrespective of ordering provider specialty, improved to 92.3%. Previously published cohort MOG-IgG PPV data is compared with our cohort results in Table 1.
Anti-dipeptidyl-peptidase-like protein 6 encephalitis with pure cerebellar ataxia: a case report
In addition to the classic triad, anti-DPPX encephalitis may manifest as mild and rare symptoms due to lower antibody titers. Fast identification of rare symptoms can help to quickly diagnosis and effective treatment.
Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management
MOGAD is now recognized to be a distinct demyelinating CNS disorder, different from MS and AQP4-IgG+NMOSD. Awareness of the clinical-MRI characteristics of MOGAD is fundamental for prompt diagnosis and treatment. The disease is defined by MOG-IgG which is a highly specific biomarker, but caution is needed with the interpretation of low titers and atypical phenotypes, as false positives can occur. Although the prognosis is generally favorable, severe residual disability can occur in MOGAD, highlighting the importance of attack prevention in patients with relapsing disease.
Immune Checkpoint Inhibitor Associated Autoimmune Encephalitis, Rare and Novel Topic of Neuroimmunology: A Case Report and Review of the Literature
This is the first case of pembrolizumab-associated AE with GAD65 and SOX1 antibodies, characterized by progressive cerebellar ataxia. It should be noted that this patient received IVIg therapy for AE and continuous pembrolizumab therapy without suspension of tumor treatment. At present, the treatment of ICI-associated AE needs to be more individualized with close monitoring, evaluation, and prudent decision-making. Finally, the mechanisms, clinical features, and treatment of ICI-associated AE are a new concept in the field of neuroimmunology, and further studies are needed.
GABAA receptor and anti-titin antibody encephalitis in a patient with thymoma
A case of a 73-year-old male with AE associated with thymoma secreting both anti-GABAaR and anti-titin antibodies. Clinical presentation included status epilepticus, behavioural changes and cognitive decline. While the status was stopped with lacosamide, AE treatment included first- and second-line immunomodulation, in addition to thymoma’s removal. Nonetheless, the patient experienced a worsening in cognitive and behavioural status.
Seronegative Autoimmune Encephalitis: A Challenge for the Neurologist
Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings
Conclusion AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.
Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis
The present study demonstrated that patients with KLHL11-Abs share a homogeneous clinical phenotype, whose main features are summarized in the newly designed MATCH score, which can be used by clinicians to select the patients that need to be tested for KLHL11-Abs. The pathological substrate is represented by an active T-cell inflammation at the primary tumour that leads to regression, in association with chronic, exhausted, inflammation in the brain with massive Purkinje cell loss, which probably explains the treatment-refractory nature of this syndrome.
New antibody identified: ZSCAN1 autoantibodies are associated with pediatric paraneoplastic ROHHAD
Our results support the notion that tumor-associated ROHHAD syndrome is a pediatric PNS, potentially initiated by an immune response to peripheral neuroblastic tumor. ZSCAN1 autoantibodies may aid in earlier, accurate diagnosis of Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) syndrome, thus providing a means toward early detection and treatment. This work warrants follow-up studies to test sensitivity and specificity of a novel diagnostic test. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches for detecting novel PNS subtypes.
Another exciting, novel autoantibody discovery. One impactful conclusion is the key value of human tissue: this antibody is not detectable in rodents.
Adenylate kinase 5 (AK5) autoimmune encephalitis: Clinical presentations and outcomes in three new patients
Adenylate kinase 5 (AK5) antibodies are biomarkers of a poorly responsive to immunotherapy, non-paraneoplastic, autoimmune limbic encephalitis. We detected 6 patients (all female, median age: 72 years [49-80]) with identical CSF antibody staining by indirect immunofluorescence on mouse tissues. We identified AK5 as the antigen and confirmed with standardized assays. Three patients with clinical information had limbic encephalitis, inflammatory CSF and mesiotemporal lobe T2 hyperintensities that evolved to atrophy on brain MRI. One patient had burning smell sensation with no evidence of seizures. Despite immunotherapy, minimal improvement was noticed in one patient; all had severe memory deficits remaining.
Anti-GFAP Antibody-Associated Hypertrophic Pachymeningitis
The present study suggests that HP may be one of the clinical phenotypes for autoimmune GFAP astrocytopathy or GFAP antibody is a biomarker for HP.
SCLC and anti-GABABR encephalitis: A retrospective analysis of 60 cases in China
Anti-gamma aminobutyric acid B receptor (anti-GABABR) encephalitis is a rare autoimmune neurological syndrome observed in lung cancer patients. A total of 60 cases of SCLC and anti-GABABR encephalitis were analyzed in the study. The clinical characteristics of SCLC and anti-GABABR encephalitis are seizures, cognitive impairment, and psychiatric disorders which affect middle-aged to elderly men in China. The long-term prognosis is relatively poor.
Seronegative Autoimmune Encephalitis: A Challenge for the Neurologist
The Antibody Prevalence in epilepsy and encephalopathy score [APE2] is an invaluable bedside clinical scoring system to estimate the probability of an autoimmune etiology in antibody negative patients.
An APE score of 4 or more indicates the necessity for antibody testing. The Response to immunotherapy in epilepsy and encephalopathy score [RITE2] score was derived from the analysis of retrospective studies to identify patients of autoimmune etiology who respond to immunotherapy (Table 1B). A score less than 7 is associated with refractoriness to immunotherapy. The combined use of both these scales enables clinicians to apply an efficient evidence-based approach for the diagnosis of autoimmune neurological diseases that require further evaluation and treatment.
Young children and the elderly are the vulnerable members of our society who are susceptible to antibody mediated illnesses and the neurocognitive outcome depends on the speed of instituting immunotherapy and disease modifying agents. These clinical rating scales are of immense importance to improve functional outcome and to achieve complete remission in patients affected with autoimmune neurological diseases.
Rare antibodies causing autoimmune encephalitis
Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis
This study demonstrated that patients with KLHL11-Abs share a homogeneous clinical phenotype, whose main features are summarized in the newly designed MATCH score, which can be used by clinicians to select the patients that need to be tested for KLHL11-Abs. The pathological substrate is represented by an active T-cell inflammation at the primary tumour that leads to regression, in association with chronic, exhausted, inflammation in the brain with massive Purkinje cell loss, which probably explains the treatment-refractory nature of this syndrome.
Unique neurologic symptoms lead to surprising cancer diagnosis
Personal story of a patient with the newly identified Kelch-11 antibody.
A team of scientists from Mayo Clinic and two other institutions published a study in 2019 that showed the existence of an autoimmune disorder that affects men. The disorder causes the immune system to attack the brain, causing severe neurologic symptoms.
That’s what happened to a Florida man, and his search for answers led him to experts at Mayo Clinic.
First test to detect recently discovered autoimmune disease associated with testicular cancer
testicular cancer–associated paraneoplastic encephalitis. The test, available nationally and internationally, detects the Kelch-like protein 11 antibody, or KLHL11, and is a result of the breakthrough study from 2019 that discovered the disease. This test has already provided patients, such as Steven Wopperer of Temecula, California, a diagnosis after he struggled for three years to find an answer to his vision and balance problems.
Successful treatment of spinal inflammation in kids
Investigation of anti-IgLON5-induced neurodegenerative changes in human neurons
Conclusions Pathological anti-IgLON5 antibodies induce neurodegenerative changes in human neurons along with increased accumulation of p-Tau. The findings support the hypothesis that these antibodies are causative for the neurodegenerative changes found in patients with anti-IgLON5-mediated autoimmune encephalitis.
Long-term Outcomes in Patients With Myelin Oligodendrocyte Glycoprotein Immunoglobulin G–Associated Disorder
Data on long-term outcomes of patients with myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG)–associated disorder (MOGAD) are scarce. We report outcomes in a single-institution cohort with long-term follow-up.
We retrospectively identified 11 adult and 18 pediatric (onset age younger than 18 years) Mayo Clinic patients from January 1, 2000, through May 31, 2019, with (1) MOGAD clinical phenotype; (2) MOG-IgG 1 seropositivity (median titer, 1:100; range, 1:20-1:1000; 8 of 13 serial samples persistently positive) and (3) 9 or more years’ follow-up from onset.
Figural Memory Impairment in Conjunction With Neuropsychiatric Symptoms in IgLON5 Antibody-Associated Autoimmune Encephalitis
Conclusions: Our findings broaden IgLON5 disease’s clinical spectrum to include predominant and discrete figural memory impairment together with sleeping dysfunction at disease onset. In addition, our report illustrates how important taking an elaborated diagnostic approach is to assuring an accurate diagnosis and the appropriate therapy if a patient presents with a persisting figural memory impairment and sleeping abnormalities so as to avoid overlooking IgLON5 disease and a potentially poor outcome.
Neurological accompaniments and outcomes in 20 patients. IgLON5-IgG is diagnostic of a potentially treatable neurological disorder, where autoimmune clues are otherwise lacking.
Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients
Improvement in recurrent anti-myelin oligodendrocyte glycoprotein antibody - positive cerebral cortical encephalitis not requiring anti - inflammatory therapy following the decrease in cytokine/chemokine levels
Clinical Reasoning: A middle-aged man with new onset seizures and myoclonic jerks
Distinctive Magnetic Resonance Imaging Findings in IgLON5 Antibody Disease
Neuropathological criteria of anti-IgLON5-related tauopathy
Autoimmune septin-5 cerebellar ataxia
Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer
In patients with neurologic symptoms of unknown cause detection of Zic4 antibodies predicts a neoplasm, usually a SCLC, and suggests that the neurologic disorder is paraneoplastic. Detection of Zic4 antibodies often associates with anti-Hu or CRMP5 antibodies. Patients with isolated Zic4 antibodies are more likely to develop cerebellar dysfunction than those with concurrent immunities.