Limbic encephalitis is a subacute progressive disorder characterized by disturbances in memory and behavior along with seizures. Antibodies against leucine-rich glioma-inactivated 1 (LGI1) are associated with a subtype of encephalitis which along with the abovementioned symptoms is also characterized by severe pain and autonomic dysfunction. The classical radiological presentation of LGI1 encephalitis is that of amygdala and hippocampal enlargement unilaterally or bilaterally with a T2 hyperintensity. Extratemporal involvement is considered a rare feature.
We present the only known case in our knowledge of anti-LGI1 encephalitis in a 47-year-old male presenting as dorsal root ganglia and spinal nerve enhancement on imaging.
Clinicians should be aware of this atypical presentation and consider anti-LGI1 encephalitis as a possible diagnosis when presented with such a neuroradiological feature.
Voltage-gated potassium channel (VGKC) antibodies are known to cause a large spectrum of rare neurological syndromes including neuromyotonia, Morvan’s syndrome, and autoimmune limbic encephalitis . Limbic encephalitis is characterized by a subacute progressive disease which is highlighted by progressive disturbance of memory and behavior along with seizures.
Interestingly, patients with VGKC associated limbic encephalitis are found to have antibodies against the protein subunit in VGKC such as leucine-rich glioma-inactivated 1 (LGI1) and to contactin-associated protein-like 2 (Caspr2) and not to VGKC per se [2, 3]. This has led to the categorization of this disease entity into three types: anti-LGI-1 encephalitis, anti-Caspr2 encephalitis, and VGKC-positive patients without LGI1 and Caspr2 antibodies. Patients with anti-LGI encephalitis often present with faciobrachial dystonic seizures, memory issue, severe pain, and autonomic dysfunctions [4,5,6]. The electrodiagnostic studies in patients with anti-LGI are often found to be normal, and pain is thought to be related to small fiber neuropathy. Here, we report a case of a patient with LGI1 antibodies who presented with neuropathic pain and showed bilateral enhancement of dorsal root ganglia on cervical spinal imaging. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
A 47-year-old male presented with subacute onset of cognitive decline, behavioral changes along with staring spells. The patient was initially evaluated at outside facility, subsequently diagnosed with epilepsy, and treated with valproic acid. Three months later, there was change in semiology of the seizures and increase in frequency of seizures despite being on maximum dose. After a prolonged seizure, he was brought to our hospital for an evaluation. During the initial neurological examination, he was alert and nonverbal, and catatonic features were noted in all four limbs. Initial evaluation includes routine blood workup, complete blood count (CBC), comprehensive metabolic panel (CMP), erythrocyte sedimentation rate (ESR), blood culture, urine analysis, meningitis panel, comprehensive drug screen, cryptococcal antigen testing, and cerebrospinal fluid (CSF) analysis which were found to be unremarkable. EEG showed intermittent right temporal slowing suggesting of neuronal dysfunction in the same region. Magnetic resonance imaging (MRI) showed mild right hippocampal atrophy. At the time of imaging, the infectious workup came back negative. The diagnosis of autoimmune encephalitis was suspected, and he was treated with immunoglobulin (IVIG) and methylprednisolone for 5 days that significantly improved his cognition and seizure free at the time of discharge. His paraneoplastic panel later came positive for anti-leucine-rich glioma-inactivated 1 (LGI1) antibody and voltage-gated potassium channel (VGKC) antibody, thus confirming the diagnosis of anti-LGI1 encephalitis. At the 4-month follow-up, he continues to show improvement with cognition and seizures were well controlled with immunotherapy and antiepileptic medications. However, the patient continues to complain of aching and burning pain which predominately involves bilateral upper extremities when compared to lower extremities despite being on medications such as pregabalin, gabapentin, duloxetine, and opioids. The patient underwent magnetic resonance imaging (MRI) at the University of Missouri Health Care System using a 1.5-T Aera MRI scanner and a standard 20-channel phase head/neck trim coil. High-resolution images were obtained via three-dimensional T1-, T2-, and T2 STIR-weighted images with a thickness of 5 mm. The MRI showed bilateral enhancement of dorsal root ganglia from C3–C7 spinal level as shown in Figs. 1a–c and 2a, b. He is currently on a monthly IVIG infusion of 1 g/kg infused over 2 days to prevent disease relapse and continues to have nociceptive pain despite being on immunomodulation therapy along with multiple neuropathic medications and interventional pain procedures. Immunosuppressive therapy was deferred due to a history of hepatitis B. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. Case reports are exempt from institutional review board (IRB) approval in our institute.
VGKC are transmembrane channels with their components situated both in the central nervous system (CNS) and peripheral nervous system (PNS). Together with proteins, they form VGKC complexes which are then involved in the regulation of cellular action potentials .
LGI1 is one such protein which forms a VGKC complex. It is a glycoprotein which is expressed primarily in the hippocampal and temporal region and is associated with the members of the ADAM family (a metalloproteinase and disintegrin family) . After forming a complex with presynaptic VGKC, it antagonizes the release of postsynaptic AMPA-receptor neurotransmitter . This interaction becomes dysfunctional in cases where antibodies are directed against LGI1 which result in the overstimulation of AMPA receptors which is the pathophysiological basis of LGI1 encephalitis. Both these autoimmune entities that are associated with immunoglobulins directed towards nodal and paranodal components are also associated with pain which is typically neuropathic in nature .
The typical radiological features of VGKC encephalitis include unilateral or bilateral amygdala and hippocampal enlargement with T2 hyperintensity at some point during the disease. Mild ill-defined enhancement and restricted diffusion were reported in 25% and 50% of the patients, respectively, with rare reports of extratemporal involvement. However, mesial temporal sclerosis is seen in the long run in as much as 50% of the patients .
Dorsal root enhancement is considered a characteristic finding in patients with nerve root irritation by herniated disc arachanoiditis or prior to surgery, infection, neoplasia and inflammatory neuropathies, and hypertrophic polyneuropathies [12, 13]. This is to our knowledge the only case report of dorsal root enhancement in a patient with anti-LGI1 encephalitis.
Availability of data and materials
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Case reports are exempt from IRB approval in our institution which is why no IRB approval was taken.
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Written informed consent was obtained from the patient for the publication of this case report and accompanying images.
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