Voltage Gated Potassium Channel antibody mediated Auto immune encephalitis

1. Faciobrachial dystonic seizures
Dr D M W Dharmakeerthi
Specialist Registrar Clinical Neurophysiology
Queen Square London

3. • 63 years old police officer presented with a history of four weeks of
brief episodes, each lasting for less than 10 seconds of jerking
movements of right hemi face and right arm occasionally precipitated
by startle.
• 48 years old lady right side facial twitching with associated short term
memory problems, low mood and vagueness of speech. The fingers of
the right hand is going in to spasms so that it mimic closed beak of a
bird. The frequency of these attacks were 7-8 per day. Rising
epigastric sensation followed by head go blank.

4. Faciobrachial dystonic seizures (FBDS)
• Adults ( Mean – 58 / youngest seen 28 years)
• Frequent (6 – 360/day)
• Brief (seconds)
• Dystonic (Ipsilateral face grimacing and arm posturing)
• Stereotyped
• Precede the cognitive impairment

5. Other features
• Alteration of awareness
• Vocalization
• Falls due to leg involvement
• Electric like epigastric sensation
• Piloerection and pupillary changes
• Stimulus sensitivity

8. • FBDS as a prodrome of Limbic encephalitis (LE) associated with
antibodies (Abs) to the voltage-gated potassium channels (VGKCs)
• VGKC complex antibodies such as
- leucine-rich glioma inactivated-1 (Lgi1)3,4
- contactin-associated protein 2 (Caspr2),3

10. FBDS features in the study group
• N = 29 – 26 developed LE
- 3 no LE
• Median age – 64 (36 – 83)
• M:F – 19:10
• Seizure frequency – 50 (6- 360) per day
• Seizure triggers – Auditory – 8
- Emotion – 6

11. FBDS as a Clinically Identifiable Prodrome
to Limbic Encephalitis
• Twenty of the other 26 (77%) patients with LE developed FBDS before
the onset of amnesia and confusion, with a median lag of 36 days
• Three patients (10%) never experienced LE.
• There were no clinically identifiable triggers for the apparent switch
from a period of FBDS alone to the development of (often dense)
amnesia
• The majority of patients had FBDS that increased in frequency until
they reached a maximum at around the time of onset of LE

12. • The LE was similar to that described previously, with
amnesia (100%)
confusion (88%)
hallucinations (35%)
sleep disturbances (31%), including REM behavior disorder, hypersomnolence, and insomnia
• During the period of LE 70% patients also developed other nondystonic seizure types, including
- generalized tonic-clonic seizures
- typical complex partial medial temporal lobe seizures
- simple partial seizures with piloerection

13. Investigations During FBDS with out cognitive impairment
• MRI – normal 9/9 (100%)
• Serum sodium – normal 13/13 (100%)
• Positive VGKC ab for LGi1 (3/4)
• EEG demonstrated ictal epileptiform abnormalities in 24%
- temporal
- frontal
- fronto-temporal

15. Investigations during and after LE
• VGKC-complex Abs
- Lgi1antibody positive – 88%
- (12% also had Caspr2 antibodies)
- No VGKC-complex–specific target determined – 12%
• Serum sodium <135mmol - 88%

16. EEG during LE
• Interictal EEG abnormalities (65%) included
- diffuse mild slowing
- bilateral frontotemporal slowing
- temporal sharp waves
• No EEG abnormalities in 35% of patients

17. Imaging
• Normal brain MRI - (46%)
• Bilateral and unilateral medial temporal lobe high T2 signal changes
(50%) and caudate/putamen (4%)
• PET showed altered glucose metabolism in the temporal region and
basal ganglia
• SPECT showed hypometabolic and hyperperfusion in the temporal
lobe

18. Typical medial temporal lobe high signal
from magnetic resonance imaging (MRI) is
shown during periods of amnesia

19. PET and SPECT images in 7 patients showed
basal ganglia and temporal lobe
abnormalities, which included
(E) temporal lobe PET bilateral
hypermetabolism
(F) right hypometabolism
(G) SPECT left hypoperfusion
Three examples of metabolic changes within
the basal ganglia are shown in H and I
(bilateral hypermetabolism) and J (left
hypermetabolism)

20. Response to Treatments
• AED effect on FBDS frequency was generally poor, and only 14%
showed a good (20–50%) or excellent (>50%) reduction in FBDS
frequency within 1 month of treatment
• FBDS response to immunotherapy was excellent
- Iv Ig
- PE
- Steroids (IV/oral)
- Rituximab

22. • There was an excellent correlation between seizure reduction and fall
in VGKC-complex Abs
• Relapses are not common in VGKC-complex Ab-associated LE.
However, 15% of these patients relapsed after weaning prednisolone
from 50 to 60mg down to 30mg over 3 months or after IvIg only.
• The FBDS were highly responsive to reinstitution of prednisolone

23. Follow up
• No patient has developed a tumor after a median follow-up of 2.75
years (range, 0.5–8 years)

26. • JAMA Neurol. 2014 Jan;71(1):79-82. doi:
10.1001/jamaneurol.2013.5179.
• Limbic encephalitis associated with anti-voltage-gated potassium
channel complex antibodies mimicking Creutzfeldt-Jakob disease.
• 58-year-old man who had a rapid onset of progressive confusion,
twitching of the face and hand, and abnormal basal ganglia detected
by magnetic resonance imaging. His conditions were initially
diagnosed as Creutzfeldt-Jakob disease (CJD). Faciobrachial dystonic
seizures, possibly pathognomonic for the VGKCC syndrome, had been
misdiagnosed as myoclonus. Treatment led to a complete resolution
of his symptoms.

27. • Arch Neurol. 2008 Oct; 65(10): 1341–1346.
• Voltage-Gated Potassium Channel Autoimmunity Mimicking
Creutzfeldt-Jakob Disease
• Clinical, radiologic, electrophysiologic, and laboratory findings in VGKC
autoantibody–associated encephalopathy may be confused with
those of CJD. Serologic evaluation for markers of neurologic
autoimmunity, including VGKC autoantibodies, may be warranted in
suspected CJD cases.

28. Summary
• FBDS as a prodrome of Limbic encephalitis (LE) associated with
antibodies (Abs) to the voltage-gated potassium channels (VGKCs)
• Clinical identification is very important as the yield of intraictal EEG is
only 24%
• Gives a therapeutic window for immunotherapy which will prevent
sequelae (cognitive impairment and cerebral atrophy)
• Well-established immunotherapy-responsive condition
• Usually without an associated tumor