Abstract
A wide variety of clinical syndromes has been associated with antibodies to voltage-gated potassium channels (VGKCs). Six years ago, it was discovered that patients do not truly have antibodies to potassium channels, but to associated proteins. This enabled the distinction of three VGKC-positive subgroups: anti-LGI1 patients, anti-Caspr2 patients and VGKC-positive patients lacking both antibodies. Patients with LGI1-antibodies have a limbic encephalitis, often with hyponatremia, and about half of the patients have typical faciobrachial dystonic seizures. Caspr2-antibodies cause a more variable syndrome of peripheral or central nervous system symptoms, almost exclusively affecting older males. Immunotherapy seems to be beneficial in patients with antibodies to LGI1 or Caspr2, stressing the need for early diagnosis. Half of the VGKC-positive patients lack antibodies to both LGI1 and Caspr2. This is a heterogeneous group of patients with a wide variety of clinical syndromes, raising the question whether VGKC-positivity is truly a marker of disease in these patients. Data regarding this issue are limited, but a recent study did not show any clinical relevance of VGKC-positivity in the absence of antibodies to LGI1 and Caspr2. The three VGKC-positive subgroups are essentially different, therefore, the lumping term 'VGKC-complex antibodies' should be abolished.
Highlights
A wide variety of clinical syndromes has been associated with antibodies to voltage-gated potassium channels (VGKCs)
Subsequent investigations demonstrated that the antibodies were not directed to the VGKC itself, but to associated proteins, which are included in the VGKC-test. Two of these proteins were identified in 2010: leucine-rich glioma-inactivated1 (LGI1) and contactin-associated protein-like 2 (Caspr2) [5,6]. This major step forward enabled the distinction of three VGKC-positive subgroups: anti-LGI1 patients, anti-Caspr2 patients and VGKC-positive patients lacking both antibodies
The third section reviews the group of VGKC-positive patients lacking antibodies to LGI1 and Caspr2
Summary
LGI1 is a secreted protein, mainly present in the hippocampus and the temporal cortex. 250 anti-LGI1-encephalitis patients have been reported so far. Major underdiagnosis of this relatively ‘new’ disease entity is suspected, as we have seen a serious increase in incidence over the last few years (own observation). Very specific for LGI1-encephalitis, but only present in half of the patients, are faciobrachial dystonic seizures (FBDS), referred to as tonic seizures [17,18]. In a series of five patients treated with rituximab marked improvement was seen in only one patient This disappointing outcome might be due to the long delay until start of rituximab (median 414 days) [23]. Relapse rate of anti-LGI1 encephalitis ranges between 0–20%, but will probably increase with extended follow up [6,16,22].
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