Emerging psychiatric syndromes associated with antivoltage-gated potassium channel complex antibodies

Abstract

Antibodies against the voltage-gated potassium channel (VGKC) were first recognised as having a potential pathogenic role in disorders of the central nervous system in 2001, with VGKC antibodies described in patients with limbic encephalitis, and the subsequent seminal paper describing the clinical phenotype and immunotherapy treatment responsiveness in 13 patients with VGKC antibodies and limbic encephalitis in 2004. These initial case descriptions were of a progressive neuropsychiatric syndrome with abnormalities of mood, sleep and cognition recognised alongside the neurological symptoms of seizures and autonomic instability. The clinical syndromes associated with VGKC complex (VGKCC) antibodies have broadened considerably over the last 15 years, with multiple cases of more restricted 'formes fruste' presentations associated with VGKCC antibodies being described. However, the relevance of antibodies in these cases has remained controversial. The understanding of the pathogenic nature of VGKC antibodies has further advanced since 2010 with the discovery that VGKC antibodies are not usually antibodies against the VGKC subunits themselves, but instead to proteins that are complexed with the potassium channel, in particular leucine-rich, glioma-inactivated protein 1 (LGI1) and contactin-associated protein 2 (Caspr2). Antibodies against these proteins have been associated with particular, although overlapping, clinical phenotypes, each also including neuropsychiatric features. Our aim is to critically review the association between VGKCC, LGI1 and Caspr2 antibodies with isolated psychiatric presentations-with a focus on cognitive impairment, mood disorders and psychosis. We recommend that screening for VGKCC, LGI1 and Caspr2 antibodies be considered for those with neuropsychiatric presentations.

Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations

“…The recommendations worked out here for Abs assessment and respective diagnostic and therapeutic consequences in schizophreniform psychoses were based on consensus from emerging clinical evidence rather than from systematic randomized studies as is the case with the present recommendations for diagnosis and treatment of AE [31]. Beyond, it should be recognized that indeed both well-established clinical terms (like encephalitis, encephalopathy, neuroinflammation) and newly proposed terms (such as AP, AE) are hardly exactly defined, thus for clinical use typically represent just clinical case definitions based on respective Table 3 The most important known autoantibodies that can be associated with symptoms of schizophreniform psychoses [9,15,31,34,36,37,38,48,63,71,79,81,82,84,85,90 limited and steadily emerging clinical consensus [6,12]. In addition, the possibility of underlying so far not identified new Abs is also limiting the whole issue.…”

Autoimmune Enzephalitiden – diagnostischer und therapeutischer Entscheidungsbaum aus psychiatrischer, neurologischer und ethisch-juristischer Sicht

“…Da diese nicht so leicht zu finden sind, wäre es sinnvoll, den Richtern einige Adressen von AIE-Experten zur Verfügung zu stellen. Des Weiteren sollten Ärzte den Richtern die wichtigsten Leitlinien, Konsenspapiere und Übersichtsarbeiten zur Verfügung stellen [7,8,16,17,21,25].…”

Innate and adaptive immunity in human epilepsies

“…Seizures are either focal in the early stages (FBDS or stereotypic focal seizures with dyscognitive or autonomic features) or generalized tonic–clonic, a late symptom as part of an LE. With the onset of LE, memory loss, confusion, and personality changes are frequent . Mild to moderate hyponatremia (115–130, most over 125 mmol/L) is present at onset in two thirds of patients.…”

“…With the onset of LE, memory loss, confusion, and personality changes are frequent. 70 Mild to moderate hyponatremia (115-130, most over 125 mmol/L) is present at onset in two thirds of patients. The outcomes can be serious, as 65% of patients have persistent mild to severe cognitive deficits.…”