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 alpha-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.
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.
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