Faciobrachial dystonic seizures

Dr D M W DharmakeerthiSpecialist Registrar Clinical Neurophysiology

Queen Square London

• 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.

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

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

• 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

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

FBDS as a Clinically Identifiable Prodrometo 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

• 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

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

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%

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

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

Typical medial temporal lobe high signal

from magnetic resonance imaging (MRI) is shown during periods of amnesia

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)

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

• 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

Follow up• No patient has developed a tumor after a median follow-up of 2.75

years (range, 0.5–8 years)

• 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.

• 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.

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