Patients presenting with subacute
amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses,
herpes simplex encephalitis, Korsakoff's syndrome and
limbic encephalitis should be considered.
Limbic encephalitis is typically a
paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important.
Voltage-gated potassium channel antibodies (VGKC-Ab) have recently been reported in three cases of reversible
limbic encephalitis. Here we review the clinical, immunological and neuropsychological features of 10 patients (nine male, one female; age range 44-79 years), eight of whom were identified in two centres over a period of 15 months. The patients presented with 1-52 week histories of
memory loss,
confusion and
seizures. Low plasma
sodium concentrations, initially resistant to treatment, were present in eight out of 10. Brain MRI at onset showed signal change in the medial temporal lobes in eight out of 10 cases. Paraneoplastic
antibodies were negative, but VGKC-Ab ranged from 450 to 5128 pM (neurological and healthy controls <100 pM). CSF
oligoclonal bands were found in only one, but bands matched with those in the serum were found in six other patients. VGKC-Abs in the CSF, tested in five individuals, varied between <1 and 10% of serum values. Only one patient had
neuromyotonia, which was excluded by electromyography in seven of the others. Formal neuropsychology testing showed severe and global impairment of memory, with sparing of general intellect in all but two patients, and of nominal functions in all but one. Variable regimes of
steroids,
plasma exchange and
intravenous immunoglobulin were associated with variable falls in serum VGKC-Abs, to values between 2 and 88% of the initial values, together with marked improvement of neuropsychological functioning in six patients, slight improvement in three and none in one. The improvement in neuropsychological functioning in seven patients correlated broadly with the fall in
antibodies. However, varying degrees of cerebral
atrophy and residual
cognitive impairment were common. Over the same period, only one paraneoplastic case of
limbic encephalitis was identified between the two main centres. Thus, VGKC-Ab-associated
encephalopathy is a relatively common form of autoimmune, non-paraneoplastic, potentially treatable
encephalitis that can be diagnosed by a serological test. Establishing the frequency of this new syndrome, the full range of clinical presentations and means of early recognition, and optimal
immunotherapy, should now be the aim.