An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis

Wong, Sui; Saunders, Michael D.; Larner, A. J.; Das, Kumar; Hart, Ian

doi:10.1136/jnnp.2009.178293

Cited by 100 publications

(78 citation statements)

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“…Though evidence is limited as to the optimal treatment regimen, most patients respond well to initial treatment with corticosteroids, plasma exchange, or IVIg, with maintenance options including corticosteroids or steroid-sparing agents such as mycophenolate, rituximab, or cyclophosphamide. 6,7,10 …”

Section: Discussionmentioning

confidence: 99%

Clinical Reasoning: A 72-year-old man with rapid cognitive decline and unilateral muscle jerks

Duncan¹,

Cholfin²,

Restrepo³

2014

Neurology

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A 72-year-old man presented with cognitive decline and unilateral muscle jerks. Three months prior to presentation, the patient suddenly developed violent muscle jerks involving the right side of his body and face that impaired his gait and balance. Approximately 1 week later, he acutely developed confusion and memory loss. Over the following weeks, he experienced fluctuating symptoms of confusion, memory impairment, insomnia, and paranoid delusions. His muscle jerks and unstable gait were intermittent with return to baseline in between attacks, but they increased in frequency and occurred many times throughout the day. He was found to be mildly hyponatremic and was eventually admitted to a psychiatric ward for treatment of acute psychosis.The patient's medical history was significant for hypertension, well-controlled diabetes, and a myocardial infarction 22 years previously. He was a retired mechanical engineer and was physically active prior to the onset of symptoms.On neurologic examination, the patient was alert and oriented to person only. He registered 3 items but was unable to recall them at 5 minutes and was unable to complete serial 7s. He had no language deficits and could follow 3-step commands without difficulty. His cranial nerve, motor, and sensory examination results were normal. He had a wide-based gait with prominent right lateral pulsion and retropulsion, without any observed muscle jerks during gait examination. Occasional myoclonus involving the right side of his face and right upper extremity were observed, which were associated with loss of awareness and dystonic posturing of the right arm.The patient was admitted to the general neurology ward and an MRI of the brain was performed (figure).

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Section: Discussionmentioning

confidence: 99%

Clinical Reasoning: A 72-year-old man with rapid cognitive decline and unilateral muscle jerks

Duncan¹,

Cholfin²,

Restrepo³

2014

Neurology

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“…One option is the use of traditional immunological approaches-the use of " broad" immunosuppressors, of intravenous immunoglobulins, or of apheresis techniques aimed at reducing antibody levels in the bloodstream-and, indirectly, via the subsequent establishment of a new diffusion equilibrium, the CNS. Whereas a combination of immunoglobulins, cyclophosphamide, and methylprednisolone is of limited effect on conditions with onconeural antibodies, similar immunological polytherapies-partly including apheresis techniques-led to rapid improvements in patients with antibodies to surface antigens, such as the VGKC complex [88,89]. Based on a retrospective outcome evaluation, Josep Dalmau et al [79] suggest a scheme of first-and second-line therapy for anti-NMDAR encephalitis (with removal of the tumor if it is a paraneoplastic condition).…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Epilepsies

Bien

Bauer

2014

Neurotherapeutics

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In patients with immune-associated disorders of the gray central nervous system matter (including recurrent seizures), antibodies against intracellular antigens have been discovered since the 1980s/1990s. In recent years, new antibodies against surface antigens have also been discovered. In two respects, these antibodies are even more interesting than the ones to intracellular antigens as, first, they promise a better response to immunotherapy; and, second, these antibodies contribute greatly to the understanding of the disease mechanisms. Whereas in encephalitides with antibodies against intracellular antigens, a cytotoxic T-cell-mediated response seems to be responsible for neuronal cell loss, in encephalitides with autoantibodies against surface antigens these antibodies are probably the relevant pathogenic agents in the associated disease conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D-aspartate receptors have been suggested to cause internalization and loss of these receptors without any cell destruction. This mechanism can explain the reversible functional effects caused by these antibodies. On the other hand, antibody-and complement-mediated destructive, and the irreversible effects of antibodies against the voltage-gated potassium channel antigens have been noted. These emerging findings make it plausible that immunological therapies, preferably early after characterization of the antibodies, offer opportunities to restore the health of affected patients.

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Section: B Anti-vgkc Antibody Encephalitis (Anti-vgkc Encephalitis)mentioning

confidence: 99%

“…A retrospective study (n = 14) found that combination therapy of IVIG plus steroids was superior to steroid monotherapy [64]. In an open prospective study, all patients (n = 9) improved when treated with the combination of plasma exchange, IVIG and steroid pulse therapy followed by oral steroid treatment [65].An immediate response to treatment is rarely observed; the majority of patients improve after several weeks of treatment [66]. In most cases, first a reduction in seizure frequency is noted, while cognitive deficits tend to respond much later [60].…”

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confidence: 99%

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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AbsTR Ac TParaneoplastic neurological disorders are rare and clinically heterogeneous diseases. They can affect both the central and peripheral nervous system as well as the neuromuscular junction and muscle. Neurological deficits develop in 2/3 of cases prior to cancer diagnosis. The diagnostic approach includes screening for antineuronal antibodies and a search for the underlying tumor. A prompt tumor therapy in combination with immunotherapy is the cornerstone in the management of these diseases. Due to lack of clinical trials, treatment recommendations are based on case series and expert opinions. Highdose corticosteroids, intravenous immunoglobulins and apheresis therapies are often used in the acute stage of the disease. These therapies should be started as early as possible, e. g., during tumor screening, in order to prevent irreversible damage. Long-term treatment is mostly immunosuppressive and depends on the specific paraneoplastic syndrome. Outcomes vary depending upon the prognosis of the underlying cancer and the nature of the antineuronal antibodies. Disorders with antibodies directed against antigens on the neuronal cell surface are highly sensitive to B cell-directed therapies and mostly associated with a favorable outcome. A thorough review of published data on actual treatment recommendation is provided along with discussion of currently not validated, but potentially effective new therapies. E264Ayzenberg I et al. Management of Immune-mediated Paraneoplastic … Neurology International Open 2017; 1: E264-E274 course, treatment response and prognosis of PNS [2,3]. Depending on tumor association, obligate and facultative paraneoplastic Abs are differentiated (Tab. 1).Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl. brainstem encephalitis) ▪ Limbic encephalitis ▪ Subacute cerebellar degeneration ▪ Opsoclonus-myoclonus syndrome ▪ Optic neuritis/neuromyelitis optica ▪ Myelopathy/myelitis ▪ Stiff person syndrome ▶Table 1 Paraneoplastic antibodies: associated neurological syndromes and tumors. Target antigen clinical presentation# Association with tumorObligate paraneoplastic Abs (directed against intracellular antigens; tumor association > 95 %) In this review we discuss the diagnosis and management of PNS. With regard to facultative paraneoplastic syndromes which are more frequently of autoimmune origin, such as neuromyelitis optica or myasthenia gravis, the reader should refer to pertinent reviews [5,6]. Diagnostic and Pathogenetic Significance of Antibodies to Intracellular and Surface AntigensAntibodies (Abs) to intracellular antigens or so-called "classical" Abs are almost always tumor-associated (exception: GAD-Abs). They can be associated with various tumors and a variety of neurological conditions [7]. However, a direct pathogenetic significance of these Abs has not yet been demonstrated. Abs to intracellular antigens serve as useful diagnostic markers in the targeted tumor search in PNS. Here, cell-mediated immune responses play a major p...

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An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis

Abstract: Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.

Cited by 100 publications

References 8 publications

Clinical Reasoning: A 72-year-old man with rapid cognitive decline and unilateral muscle jerks

Clinical Reasoning: A 72-year-old man with rapid cognitive decline and unilateral muscle jerks

Autoimmune Epilepsies

Management of Immune-Mediated Paraneoplastic Neurological Disorders

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