Clinical and Neurophysiological Development of Unverricht‐Lundborg Disease in Four Swedish Siblings

Abstract

Four siblings aged 12-18 years with progressive myoclonus epilepsy demonstrated a subclinical stage at the age of 9-11 years, with visual blackouts and polyspike electroencephalographic (EEG) activity on photic stimulation, an early myoclonic stage at the age of 12-15 years, with increasing segmental, stimulus-sensitive myoclonus, occasional nocturnal buildup myoclonic "cascade" seizures, slowing of EEG alpha-activity, episodic 4-6 Hz bilateral sharp waves and polyspikes with myoclonias on photic stimulation, and a disabling myoclonic stage at the age of 16-18 years, with periodic generalized myoclonias, nocturnal myoclonic "cascade" seizures, ataxia, dysarthria, mental changes, intermittent wheelchair dependency, and continuous EEG slow waves with polyspikes and intense myoclonias on photic stimulation. One of the siblings died at the age of 18 years with no apparent cause of death. Treatment with antiepileptic drugs other than valproate may have contributed but none of the siblings were ever treated with phenytoin. Extensive clinical and laboratory investigations revealed no abnormalities and excluded other known possible causes of progressive myoclonus epilepsy. The diagnosis was consistent with Unverricht-Lundborg disease and rested on typical age of onset, clinical signs, EEG, and evoked response abnormalities. Buildup myoclonic seizures are typical in advanced stages of Unverricht-Lundborg disease. We have labeled these myoclonic "cascade" seizures. A typical seizure was studied with video-EEG and cardiorespiratory monitoring. Characteristics revealed were onset with continuous arrhythmic myoclonic jerks followed by intense rhythmic myoclonus with increasing muscle tone that successively reduced the amplitude of the jerks. The EEG during the whole seizure showed intense polyspike activity. Obstructive apnea was seen at the peak of the seizure. There were no cardiac dysrhythmias. Consciousness was normal or only slightly impaired. Postictal drowsiness was not observed. Myoclonic "cascade" seizures are easily confused with generalized tonic-clonic seizures.

Progressive Myoclonus Epilepsy of Unverricht‐Lundborg Type

“…Previously, myoclonus tended to be progressive throughout life. Now advances achieved in the medical treatment of EPMl have resulted in a better outcome, and the development of myoclonus is not always progressive; it may stabilize or even improve over time (14)(15)(16).…”

Progressive myoclonic epilepsies: review of clinical, molecular and therapeutic aspects

“…The jerks are usually severe, irregular, asynchronous and predominate in the morning upon awakening, occurring in any segment of the body [1][2][3]9]. The tonic clonic seizures are very common and absence seizures have also been observed [2,9,10].…”

“…The background activity might be normal in the early years, but evolves with generalized slowing associated with epileptiform discharge bursts. Photoparoxysmal responses and photosensitivity reactions are characteristic and, unlike other PME, the sleep electroencephalographic patterns remain normal [2,10].…”

Unverricht‐Lundborg disease

“…At onset, GTCS cannot be easily differentiated from those observed in JME, and may occur without prior myoclonic jerks. However, with disease progression, they may evolve into cascade seizures (Kyllerman et al, 1991), characterized by a build-up of increasingly intense and violent myoclonic jerks, culminating into a short GTCS; some patients do not report clear consciousness and more or less retain normal contact during this type of seizure. Often, patients experience GTCS or major seizures after a period of progressive increase in myoclonus and subsequently experience less myoclonus, with a decreased risk of major seizures for a period that can last days to weeks; this periodicity has already been described by Unverricht and reported for other PMEs Vanni et al, 2014).…”