Limbic Encephalitis Presenting Research Articles

Leucine-rich Glioma Inactivated 1 (LGI-1) Limbic Encephalitis Presenting with Psychotic Symptoms without Seizures: A Case Report with Five-year Follow-up and Review of Literature.

Leucine-rich Glioma Inactivated 1 (LGI-1) Limbic Encephalitis Presenting with Psychotic Symptoms without Seizures: A Case Report with Five-year Follow-up and Review of Literature.

A Case of Limbic Encephalitis Presenting as Paraneoplastic Neurological Syndrome with Possible Involvement of Immune Checkpoint Inhibitors

A Case of Limbic Encephalitis Presenting as Paraneoplastic Neurological Syndrome with Possible Involvement of Immune Checkpoint Inhibitors

A Case of Pembrolizumab (Anti-PD-1) Induced Encephalitis

Objective N/A. Background PD-1 Immune checkpoint inhibitors (ICI) have been associated with neurologic immune-related adverse events including meningoencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of suspected pembrolizumab (anti PD-1) induced limbic encephalitis presenting as episodic aphasia. Design/Methods N/A. Results A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases post thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation surgery presented with recurrence of brain metastases one year after the diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region causing right homonymous hemianopsia. The metastases initially improved in size and number with radiation and serial brain MRIs were stable. Biopsy of the mets revealed a poorly differentiated carcinoma. He was subsequently treated with pembrolizumab for six months. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia concerning for seizures. Continuous EEG monitoring revealed a left-sided focus without seizures, and the episodes persisted despite levetiracetam and clobazam. Four lumbar punctures revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48–68 mg/dl), negative cytology, flow cytometry and viral studies including JC virus. Paraneoplastic panels in serum and cerebrospinal fluid were negative. Repeat MRIs findings were most consistent with radionecrosis and noted improvement of the metastatic lesions. Suspicion was raised for pembrolizumab-induced encephalitis and he received high-dose steroids with minimal response however, clinical improvement noted with reduced episode frequency after intravenous immunoglobulin induction therapy and rituximab maintenance therapy. Conclusions PD-1 ICI-related encephalitis is a diagnosis of exclusion that should be considered in patients with encephalopathy or other neurological deficits following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences are reported in males. Early recognition is crucial to prevent long-term neurologic damage. Outcomes are depend on patient characteristics and clinical presentation.

NCOG-38. PEMBROLIZUMAB (ANTI-PD-1) INDUCED LIMBIC ENCEPHALITIS PRESENTING AS EPISODIC APHASIA

Abstract PD-1 immune checkpoint inhibitors (ICI) have been associated with neurological immune-related adverse events including meningioencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of pembrolizumab (Anti-PD-1) induced limbic encephalitis presenting as episodic aphasia. A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases, post total-thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation presented with recurrence of brain metastasis 1 year after diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region. The metastases had initially improved in size and number with radiation, followed on serial MRI Brain - that were stable. Biopsy of recurrence revealed a poorly differentiated cancer. He was subsequently treated with pembrolizumab for 6 months for refractory carcinoma. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia, initially concerning for seizures. Continuous EEG monitoring revealed non-epileptogenic left-sided foci and no seizures were captured. Patient empirically started on levetiracetam and clobazam - however, episodes persisted. Lumbar puncture revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48-68 mg/dL), negative cytology, flow cytometry, and viral studies including JC virus. Paraneoplastic panel in serum and cerebrospinal fluid were negative. Repeat MRI findings were most consistent with radionecrosis and on contrary improvement of the previous metastatic lesions. This rose suspicion for pembrolizumab-induced encephalitis and he received high dose steroids with minimal response but great clinical improvement with IVIG and induction/maintenance therapy with rituximab. Marked reduction in aphasic episodes were noticed thereafter. PD-1 ICI-related encephalitis is diagnosis of exclusion that should be considered in patients with encephalopathy or neurological deficit following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences reported in males. Early recognition is crucial to prevent long-term neurological damage. Outcomes depend on patient characteristics and timeline of presentation.

Anti-Ma2-associated limbic encephalitis presenting with transient epileptic amnesia

Anti-Ma2-associated limbic encephalitis presenting with transient epileptic amnesia

Unusual Presentation of Paraneoplastic Limbic-Encephalitis (PLE) with Acute Retrograde-Amnesia as Presenting Symptom. (P11-1.003)

Unusual Presentation of Paraneoplastic Limbic-Encephalitis (PLE) with Acute Retrograde-Amnesia as Presenting Symptom. (P11-1.003)

Rare presentation of autoimmune limbic encephalitis with anti-Yo antibodies: Case report

Introduction: Paraneoplastic limbic encephalitis is a non-metastatic complication of malignant disease characterized by subacute neuropsychiatric symptoms and short-term memory deficits. Case: We present an atypical case of a 38-year-old, previously healthy female with recurrent seizures, severe persistent short-term memory loss, and emotional lability. The patient was diagnosed with autoimmune limbic encephalitis confirmed by magnetic resonance imaging findings and positive anti-Yo antibodies. She screened negative for occult malignancies. The patient responded to daily prednisone and intravenous immunoglobulins and her cognitive deficits were resolved. Conclusion: This is an unusual case of autoimmune encephalitis as anti-Yo antibodies are typically associated with cerebellar dysfunction. Our patient’s case adds to the one other published case showing induction of limbic encephalitis due to anti-Yo antibodies, and prompts consideration of paraneoplastic anti-Yo limbic encephalitis as a rare cause of symptoms in patients with limbic encephalitis-like symptoms and no known etiology.

Paraneoplastic Limbic Encephalitis Secondary To Mixed Non-Seminomatous Germ Cell Tumours

Abstract Casestudy: Testicular tumors account for 1–2% of all tumors in men, with 95% of these being germ cell tumors. The main risk factor for the development of testicular cancer is cryptorchidism. Paraneoplastic limbic encephalitis is a rare sequela of testicular tumor associated with anti-Ma2 and KLH11 antibodies. The most effective treatment for paraneoplastic limbic encephalitis is treatment of the primary malignancy. We present a 41-year-old male that presented to the emergency department with two weeks of episodic alteration of consciousness and memory disturbances. Negative neurologic evaluation and imaging led to concern for a paraneoplastic process from a distant malignancy. CT imaging revealed an enlarged, necrotic para-aortic lymph node and subsequent ultrasound demonstrated a right sided testicular mass. Right radical orchiectomy was performed. Microscopically, the mass consisted of mixed respiratory epithelium, gastrointestinal glands and squamous epithelium with keratinization consistent with a post-pubertal testicular teratoma with associated in-situ germ cell neoplasia. Resection of the para-aortic mass revealed large anaplastic cells with epithelioid features, nuclear pleomorphism and frequent mitoses. Immunostaining was positive for Pan-Keratin and OCT4, consistent with poorly differentiated embryonal carcinoma. Resection of the primary and metastatic disease, as well as treatment with corticosteroids resulted in resolution of the encephalitis. This presentation of severe neurological disturbances in the setting of a metastatic mixed nonseminomatous germ cell tumor represents a rare presentation of paraneoplastic limbic encephalitis.

Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report

BackgroundLimbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors.Case presentationWe present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance.ConclusionsThis case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of “idiopathic” optic neuritis in the Chinese population.

Disseminated herpes simplex virus 2 (HSV-2) encephalitis in a liver transplant recipient: Potential implications for liver transplant programs

Herpes simplex virus type 2 (HSV-2) is a rare cause of herpes encephalitis. We report a case of severe right limbic encephalitis presenting as an altered level of consciousness in a post-liver transplant adult man. HSV-2 was identified by polymerase chain reaction in the cerebrospinal fluid (CSF). Concurrent active perineal skin eruptions were positive for HSV-2, confirming the theory of disseminated HSV-2 from genitals to brain. Intravenous acyclovir was given for 3 weeks. Although the outcome was an improved level of consciousness, the patient was left with significant residual neurological morbidity. Our experience emphasizes the importance of HSV prophylaxis in those with positive serostatus pre-transplant, and not on cytomegalovirus (CMV) prophylaxis in the immediate post-transplant period. We also recommend stringent pre-transplant assessment, including specific and direct questioning of candidates regarding a history of sexually transmitted infections (STIs), a determination of HSV serostatus, and the examination and testing of any suspicious lesions.

32. Facio-brachial dystonic seizures in LGI1 Limbic Encephalitis: Analysis of video EEG monitoring in a small group of patients

Leucine-rich glioma inactivated 1(LGI1) antibodies are frequently associated with a common form of limbic encephalitis (LE) presenting with cognitive impairment, tonic-clonic and distinctive facio-brachial dystonic seizures (FBDS), not related with a specific EEG pattern. We describe clinical-EEG features of three patients with LGl1-LE with different response to immunotherapy. Three pts, admitted to our Neurology department for LE with positive test for LGI1 antibodies, performed video-EEG monitoring and immunotherapy. Video and still images showed frequently (3–40 episodes/day) paroxysmal brief events characterized by facial grimacing and sometimes dystonic arm posturing, with alternating side, suggestive for FBDS. We observed electrodecremental events (EDEs) or a contralateral slow-wave before “dystonic seizures” but not a clear ictal-EEG pattern. In all of the patients interictal EEG was normal. Furthermore, Video-EEG monitoring revealed multiple daily electrographic temporal seizures. Immunotherapy were associated with control of FBDS in two of three presented patients, with different latency. Video-EEG monitoring of our LGI1-LE patients showed frequent FBDS and bilateral temporal seizures. The lack of a clear ictal-EEG pattern for FBDS and the positive response to immunotherapy, support the hypothesis that dystonic episodes does not have a cortical origin, but are rather related to a possible basal ganglionic dysfunction.

Some patients with advanced malignancies also have reversible catatonia or limbic encephalitis

Two potentially treatable disorders, paraneoplastic catatonia and paraneoplastic limbic encephalitis, may be hidden within the presentation of end stage cancer patients, because catatonia and limbic encephalitis usually feature severely altered mental status, confusion, anorexia, and minimal responsiveness that are also common with people dying of cancer. If catatonia and limbic encephalitis are correctly diagnosed and treated, there should be definite and dramatic improvement that would translate into better quality of life and perhaps even resumption of cancer therapy. This editorial reviews basic features of catatonia and limbic encephalitis, and then presents a strategy to systematically screen for these in end stage cancer patients who are about to enter hospice. A protocol is outlined that could be adapted for clinical practice or for designing clinical studies.

Treatment responsive GABA(B)-receptor limbic encephalitis presenting as new onset super-refractory status epilepticus (NORSE) in a Deployed U.S. Soldier (P4.233)

Treatment responsive GABA(B)-receptor limbic encephalitis presenting as new onset super-refractory status epilepticus (NORSE) in a Deployed U.S. Soldier (P4.233)

Anti-vgkc Antibody-associated Limbic Encephalitis Presenting with Recurrent Catatonia

Limbic encephalitis is an inflammatory disorder, commonly characterized by psychiatric features and cognitive impairment. It used to be considered a rare disease, usually paraneoplastic, with poor prognosis. Recent findings of membrane-surface directed antibodies, including anti-VGKC (Voltage-Gated Potassium Channels) antibodies, showed a substantial proportion of cases with no association with any malignancy and better prognosis. A 56-year-old woman was admitted to the psychiatric ward in Nov/2007, with an acute onset of psychomotor retardation and agitation periods, apathy and nihilistic symptoms. She improved very slowly with lorazepam, clomipramine and quetiapine. In Jun/2014, she was admitted again to the psychiatric ward with acute onset of intense headache, confusion, insomnia, agitation and prejudice ideas. There was a clinical deterioration with mnesic deficits, catatonic stupor, autonomic dysfunction and seizures. Complementary exams revealed: ESR>120mm; hyponatraemia; acelular CSF with slightly elevated protein; EEG with slow base activity; Brain MRI with diffuse cortical atrophy and multiples subcortical hyperintensities of frontoparietal regions on FLAIR and T2 sequences; and positive anti-VGKC antibodies. Initially there was a poor transitory improvement with high-dose steroids and intravenous immunoglobulins. After 5 months, she did plasmapheresis with relevant clinical improvement. About 80% of anti-VGKC encephalitis patients have clinical improvement following prompt treatment. In this case, there was not as good improvement as initially expected probably because of the prolonged duration of disease prior to effective treatment. Given the good prognostic outcome with prompt initiation of immunotherapy, early recognition and diagnosis of this rare neuropsychiatric syndrome is crucial.

Autoantibody-induced encephalitis

Neurologists often encounter encephalitis caused by unknown agents. Autoantibody-induced encephalitis is a new and exciting group of disorders that must be considered in the differential diagnosis as they are reversible if treated early in the course of the disease, but fatal if unrecognized. We describe the first report from the Indian subcontinent of three rare cases of different autoantibody-induced disorders, which were successfully managed with immunosuppressive therapy resulting in a good clinical outcome. Case 1 was a young woman with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, not associated with tumor, who showed significant improvement with Rituximab. NMDA receptor encephalitis occurs typically in young females with psychiatric features, followed by an altered level of consciousness, dysautonomia, hyperkinetic movement disorder, seizures, and hypoventilation. Rituximab, which aims to suppress antibody production is an effective treatment modality. Anti-voltage-gated potassium channel antibodies (anti-VGKC-Ab) cause hyperexcitability of the peripheral nerve and central nervous system. Case 2 was a patient of limbic encephalitis presenting with complex partial seizures responding dramatically to steroids. Anti-VGKC-Ab-associated limbic encephalopathy is considered to be an autoimmune, non-paraneoplastic, potentially treatable encephalitis. The clinical features of anti-VGKC-Ab-associated limbic encephalitis are: Subacute onset of episodic memory impairment, disorientation, and agitation. Case 3 presented with Morvan's fibrillary chorea. Peripheral nerve hyperexcitability is the chief manifestation of the Morvan syndrome or cramp-fascilulation syndrome. The Morvan syndrome is characterized by neuromyotonia with autonomic and central nervous syndrome (CNS) involvement. Both VGKC-Ab-associated limbic encephalitis and Morvan syndrome can be successfully treated. Therefore, when these diseases are suspected, it is important to measure the anti-VGKC-Ab level.

Anti–Glutamic Acid Decarboxylase Antibody Associated Limbic Encephalitis in a Child

Anti-glutamic acid decarboxylase directed antibodies are a rare cause of autoimmune limbic encephalitis that is relatively resistant to immunotherapy. Here we report a 15-year-old boy with nonparaneoplastic, anti-glutamic acid decarboxylase limbic encephalitis presenting with subacute headache, memory disturbance, psychiatric symptoms, and seizures. At onset, his memory disturbance manifested as transient global amnesia-like episodes. Clinical remission was achieved with rituximab, intravenous immunoglobulin, and corticosteroids.

Anti-AMPA Receptor Limbic Encephalitis Presenting with Ovarian Teratoma, Encephalopathy and Autonomic Instability

Anti-AMPA Receptor Limbic Encephalitis Presenting with Ovarian Teratoma, Encephalopathy and Autonomic Instability

Voltage-Gated Potassium Channel Antibody Associated Limbic Encephalitis Presenting as a Rapidly Progressive, Refractory Status Epilepticus: A Case Report and Review of Literature (P07.177)

Voltage-Gated Potassium Channel Antibody Associated Limbic Encephalitis Presenting as a Rapidly Progressive, Refractory Status Epilepticus: A Case Report and Review of Literature (P07.177)

GABAB receptor antibodies in paraneoplastic cerebellar ataxia

Autoantibodies to the gamma-aminobutyric acid-B (GABAB) receptor were recently described in patients with limbic encephalitis presenting with early or prominent seizures. We report on a 64-year-old man with malignant melanoma who during adjuvant therapy with interferon (IFN)-alpha developed cerebellar ataxia. Indirect immunofluorescence on brain tissue sections revealed high-titer (1:20,000) IgG1 serum autoantibodies to the cerebellar molecular and granular layer, which were confirmed to be directed against GABAB receptor in a cell-based assay. This case highlights cerebellar ataxia in the absence of seizures as a clinical manifestation of GABAB receptor autoimmunity and extends the spectrum of tumors underlying this condition to malignant melanoma. IFN-alpha therapy may have contributed to the development of autoimmunity in this patient.

Anti–Glutamic Acid Decarboxylase Limbic Encephalitis Without Epilepsy Evolving Into Dementia With Cerebellar Ataxia

To expand the spectrum of the clinical presentation of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis and to improve the recognition of this entity. Case study. University hospital. An 11-year-old-girl with progressive mood and behavioral disorder, speech impairment, and short-term memory impairment who manifested cerebellar ataxia with nystagmus during the disease course. Blood and cerebrospinal fluid analysis including autoantibodies, electroencephalography, brain and spinal magnetic resonance imaging, and cognitive and neuropsychological assessment were performed. High-dose methylprednisolone sodium succinate pulses, cycles of intravenous immunoglobulins, mycophenolate mofetil, and rituximab as well as antipsychotics and benzodiazepine were administered. Diagnosis of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis was made. The clinical features during the first months of disease included only mood, behavioral, and memory impairment. After 5 months, despite immunotherapies, cerebellar ataxia with nystagmus appeared with brain magnetic resonance imaging evidence of cerebral atrophy. No clinical or infraclinical seizures were recorded during follow-up. Anti-glutamic acid decarboxylase antibodies-related limbic encephalitis can present with only behavioral or neuropsychological symptoms without any epileptic disorder. Moreover, cerebellar ataxia related to anti-glutamic acid decarboxylase antibodies can be observed in patients with limbic encephalitis during the disease course.