Drop attacks

Practical Implications

LGI1 autoimmune encephalitis should be considered in the differential diagnosis of patients with recurrent stereotypical spells of unclear origin, including drop attacks.

We describe a clinical manifestation of leucine-rich glioma-inactivated-1 (LGI1) encephalitis. The patient was a 90-year-old woman, independent at baseline, with a medical history of hypertension. Two months prior to admission, she had an unwitnessed fall and was found after an unknown period of unconsciousness. She was taken to an outside hospital where rhabdomyolysis (creatine kinase >16,000, reference 24–170 U/L) was documented. During that admission, she had a witnessed generalized tonic-clonic seizure. Prolonged EEG video monitoring captured multiple episodes of right leg jerking without a change in her consciousness or an abnormal EEG correlate. Interictal EEG findings were unremarkable. A metabolic panel showed mild hyponatremia (133; reference 137–145 mmol/L). MRI of the brain was unremarkable. CSF analysis was normal (leukocytes 3/mm³, protein 45 mg/dL, and glucose 80 mg/dL). She was discharged home on levetiracetam (1,500 mg daily) and did not have any further documented convulsions, but reported hypersomnolence.

A month after discharge, the patient was admitted to our center because of sudden falls that occurred daily while standing or walking. Episodes were described by the patient as “my legs are collapsing underneath me.” Neither aura nor loss of consciousness was noted. Her neurologic examination was unremarkable. The patient had no cognitive complaints and cognitive impairment was not noted by examining physicians during her admission. Cardiovascular causes were excluded. A video EEG was performed, which captured multiple spells (see video at Neurology.org/cp) without any abnormal electrographic correlate. Interictal EEG findings were unremarkable over 72 hours of recording. Two types of events were documented: episodes of sudden jaw opening with bilateral arm and leg flexion for 1–2 seconds and episodes of brief loss of muscle tone that caused her to fall forward. The former episodes were considered compatible with faciobrachial dystonic seizures (FBDS), which suggested an underlying diagnosis of LGI1 encephalitis. Levetiracetam was tapered off because of reported hypersomnolence and lamotrigine (25 mg daily) was started with a weekly titration schedule. A paraneoplastic and autoimmune panel was sent on serum, which showed high levels of LGI1 antibody (1:160, reference <1:10) and positive voltage-gated potassium channel (VGKC) antibodies (739 pmol/L, reference 0–31). Her family declined a repeat lumbar puncture, EMG, and brain MRI. Empiric treatment was started with methylprednisolone 1 g/d for 5 days. The episodes declined progressively after starting steroids. She was discharged to a rehabilitation facility after 72 hours of remission of events and had not had any further spells at the time of a 1-month follow-up visit.

DISCUSSION

The first description of FBDS related to VGKC antibodies was published in 2008. The events were characterized by unilateral or bilateral arm posturing with facial grimacing lasting less than 3 seconds without loss of consciousness. In addition to the face and arm, 30% of cases may have involvement of the leg.¹ In 2010, LGI1 antibodies were discovered and linked to these paroxysmal events. Currently, FBDS are considered pathognomonic of LGI1 encephalitis, although they are only present in fewer than 50% of cases.²

In our patient's video EEG, events 3, 4, and 5 were consistent with FBDS, as classically described. However, events 1 and 2 showed sudden loss of muscle tone while sitting without any preceding jerk or abnormal posturing. Even though falls secondary to the abnormal leg jerks of FBDS have been described,³ this patient's events of sudden postural lapses are rare in LGI1 encephalitis. Semiologically, these events resembled either atonic seizures or negative myoclonus. Atonic seizures are defined as a sudden loss of muscle tone lasting 1–2 seconds. EEG patterns related to atonic seizures include paroxysmal fast activity, spike-and-wave discharges, or diffuse attenuation⁴; none of these was documented in this case. Negative myoclonus is defined as a sudden postural lapse of less than 100–400 ms. It can have a cortical origin, in which case it is considered epileptic, or can arise from subcortical regions such as the thalamus, internal capsule, or basal ganglia.⁵

The etiology of FBDS has been controversial, with some authors suspecting a subcortical origin⁶ and others suggesting a cortical source.⁷ A subcortical origin is suspected based on the low reported prevalence of concomitant ictal abnormalities on EEG, a very poor response to antiepileptic agents, and the presence in these patients of bilateral hypermetabolism in the striatum on PET studies.⁸ However, others have reported the presence on EEG of a slow wave in frontocentral regions, which precedes the clinical event, as well as cortical hypermetabolism on PET studies.⁷

The origin of this patient's drop attacks was unclear. Concomitant EEG-EMG recordings could have been useful for further describing this phenomenon, but were not performed at the patient's request.

AUTHOR CONTRIBUTIONS

A. Vives-Rodriguez, A. Sivaraju, E.D. Louis: drafting/revising the manuscript for content, including medical writing for content, study concept or design, analysis or interpretation of data.

STUDY FUNDING

No targeted funding reported.

DISCLOSURE

A. Vives-Rodriguez and A. Sivaraju report no disclosures. E.D. Louis is Editor-in-Chief of Tremor and Other Hyperkinetic Movements and receives/has received research support from NIH/NINDS and Parkinson's Disease Foundation. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.