LETTER TO THE EDITOR
|Year : 2019 | Volume
| Issue : 1 | Page : 121-122
Leucine-Rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with adenocarcinoma of prostate: A case report
Devaraddi Navalli1, Narayan R Mutalik2, G Jayalakshmi2
1 Department of Medicine, S Nijalingappa Medical College, Bagalkot, Karnataka, India
2 Department of Psychiatry, S Nijalingappa Medical College, Bagalkot, Karnataka, India
|Date of Web Publication||26-Dec-2018|
Dr. Devaraddi Navalli
Department of Medicine, S Nijalingappa Medical College, Bagalkot, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Navalli D, Mutalik NR, Jayalakshmi G. Leucine-Rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with adenocarcinoma of prostate: A case report. Ann Indian Acad Neurol 2019;22:121-2
|How to cite this URL:|
Navalli D, Mutalik NR, Jayalakshmi G. Leucine-Rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with adenocarcinoma of prostate: A case report. Ann Indian Acad Neurol [serial online] 2019 [cited 2019 Jan 23];22:121-2. Available from: http://www.annalsofian.org/text.asp?2019/22/1/121/248513
Limbic encephalitis (LE) is an autoimmune disorder, characterized by subacute onset of short-term memory impairment, disorientation, seizures, altered consciousness, and psychiatric symptoms. It can occur as paraneoplastic syndrome with onconeural antibodies targeted against intracellular neuronal antigens, also of nonparaneoplastic origin with antibodies targeting neuronal cell surface antigens such as leucine-rich glioma-inactivated protein 1 (LGI1).
LGI1 is one of the synaptic autoantigens targeted in voltage-gated potassium channel LE. Antibodies to LGI1 produce a syndrome of LE (e.g., amnesia, confusion, hallucinations, and sleep disturbances), hyponatremia, and faciobrachial dystonic seizures. This autoimmune condition is nonparaneoplastic and highly responsive to immunotherapy, intravenous immunoglobulins, and plasma exchange, or corticosteroids should be chosen promptly for the treatment.
Anti-LGI1 encephalitis of paraneoplastic origin (20%) is rare. Among reported cases, malignant tumors of lungs, thyroid, breast, or kidney; ovarian teratoma; or thymoma have been related to the disease. LE in cases of prostate cancer and adenocarcinoma type is sparse, and to the best of our knowledge, there are five cases that have been reported previously. We herein report a case of LE associated with adenocarcinoma of prostate.
A 75-year-old male presented with a history of poorly controlled focal seizures of 8-year duration. He had multifocal myoclonic jerks, bowel and bladder incontinence, forgetfulness of subacute onset with altered behavior such as irrelevant speech, crying spells without any reason, and sleep disturbances for 3 months. He also had other comorbidities such as diabetes mellitus, hypertension, hypothyroidism, chronic obstructive pulmonary disease, old pulmonary tuberculosis, and ischemic heart disease. He was found to have prostatomegaly when he was evaluated for urinary disturbances 7 years back. He underwent bilateral subcapsular orchiectomy with transurethral resection of prostate for carcinoma prostate (adenocarcinoma acinar type, Gleason score 7) 6 months before the presentation and he was on multiple antiepileptic drugs with ongoing myoclonic jerks. On physical examination, he was drowsy; confused; not oriented to time, place, and person; afebrile; pulse 80/min; and blood pressure 130/90 mmHg. Neurological examination revealed cranial nerves were normal; bilaterally, deep tendon reflexes were elicitable and Babinski positive; Mini-Mental Status Examination score (MMSE) was 22/30. Lobe function tests showed that recent memory was impaired, his scores on tests for prefrontal cortex like attention span and number of words produced (F = 2, A = 4, S = 5) in 1 min and score on tests for abstract thinking were low, switching movements during Luria's test were slow, he had ideomotor apraxia and constructional apraxia but his right–left orientation and visuospatial functions were intact. He had hyponatremia (serum sodium 120 mg/dl), cerebrospinal fluid analysis was normal, magnetic resonance imaging (MRI) of the brain T2-weighted images [Figure 1] showed diffuse cerebral atrophy with multifocal nonspecific white matter signal changes and no signal changes were observed in bilateral medial temporal lobes in T2 fluid-attenuated inversion recovery images [Figure 2]; electroencephalography showed diffuse background slowing, LGI-1 antibody was strongly positive, contactin associated protein (CASPR) 2 was negative, glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) 1 and 2 were negative, glutamate receptor N-methyl-D-aspartate was negative, and gamma-aminobutyric acid B1 and B2 receptors were negative. A diagnosis of LGI1 antibody-positive encephalitis was made and the patient was started on intravenous methylprednisolone 1000 mg infusion pulse therapy with sodium valproate 500 mg twice daily and levetiracetam 500 mg twice daily for control of seizures. After 4 weeks, when he was readmitted for methylprednisolone pulse therapy, he was seizure free, his behavioral and mood disturbances had remitted, his MMSE score was 26. computed tomography scans of chest and abdomen were done to rule out other possible malignancies which did not detect any malignancy. He has been seizure free for the past 5 months and his cognitive level (MMSE-29) has improved though not to premorbid level since then.
|Figure 1: T2 fluid-attenuated inversion recovery magnetic resonance imaging brain axial image shows no signal changes in bilateral medial temporal lobes|
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|Figure 2: T2-weighted magnetic resonance imaging image shows diffuse cerebral atrophy with multiple nonspecific white matter signal changes|
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Anti-LGI1 encephalitis had an annual incidence of 0.83 per million people in the Dutch population in 2015. LGI1 is expressed densely in the hippocampi. LGI1 (chromosomal location 10q24) is a secreted neuronal protein and it serves as an extracellular ligand for ADAM22, which binds to PSD-95 and plays a role in synaptic transmission. During postnatal development, LGI1 mediates dendrite pruning and presynaptic and postsynaptic maturation in the hippocampus. Number of mutations of LGI1 have been reported in an inherited form of human epilepsy, autosomal dominant lateral temporal lobe epilepsy. AMPAR is also a representative autoantigen for the LE, which implies that LGI1 is essential for the normal functioning of the limbic system of the adult brain. LGI1 is involved not only in regulating brain excitability but also helps in memory formation which explains features of dementia in these patients.
In the background of myoclonic jerks occurring multiple times in a day and which were unremittent with two adequate doses antiseizure medication, our patient presented with rapidly progressive dementia associated with cognitive decline and near abrupt change in his behavior in 2–3 months, hence a range of differential diagnosis were considered. As the patient was operated for carcinoma of prostate few months back, his seizures being part of paraneoplastic syndrome became more likely. In cases of autoimmune encephalitis, neuropsychiatric symptoms were identified before a malignant disease was detected in 60% of cases. In our case too, the patient had episodic focal seizures for the past 8 years, during which time he also was treated for benign prostatic hyperplasia; later carcinoma prostate was detected on biopsy.
In cases of seizures with new-onset neuropsychiatric symptoms such as progressive dementia and behavioral and mood changes, testing of antineuronal antibodies (LGI-1 antibodies) as part of diagnostic workup will be advantageous as early diagnosis can reduce years of morbidity.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]