Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood-Report of five cases

Abstract

SUMMARYPurpose: To assess the efficacy and tolerability of chronic high-frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes. Methods: Five adult patients (four male, 28-39 years) with PME underwent chronic high-frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow-up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation-induced myoclonic jerks and daily life performance 8 weeks prior to implantation. Key Findings: Follow-up periods ranged from 12-42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side-effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic-clonic seizures increased after 3 months of stimulation following extensive traumarelated surgery. The best effect was seen in the least impaired patient. Significance: DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly. KEY WORDS: Myoclonic epilepsy, Surgery, Deep brain stimulation, Stereotaxy.According to the Proposal of the International League Against Epilepsy (ILAE) (Commission on Classification and Terminology of the International League Against Epilepsy, 1989), progressive myoclonic epilepsy (PME) syndromes are classified as relatively well-defined entities such as Unverricht-Lundborg disease or Lafora's disease. In many instances though, a more specified classification is lacking, although recent developments in molecular genetics have helped to achieve a better understanding of PME (Shahwan et al., 2005). Patients with PME usually develop highly drug-resistant and often trigger-dependent myoclonic jerks and generalized tonic-clonic seizures. The stimulus sensitivity, the severity, the frequent association with additional ataxia and fine motor skills impairment and the correlation with sleeplessness regularly lead to dramatic impairment of personal quality of life with the necessity to use helmets or wheelchairs. In addition, the course of the diseases usually progresses, so that some disorders like Lafora's disease are characterized by a very rapid deterioration with fatal prognosis, whereas other forms such as UnverrichtLundborg disease often show a slow progression with severe impairment of the patients over decades...

Safety and feasibility of nucleus accumbens stimulation in five patients with epilepsy

“…subthalamicus have been discussed as possibly effective in small uncontrolled trials [17–19]. Recently, this target has been chosen for distinct epilepsy syndromes, such as progressive myoclonus epilepsy [18] and epilepsy due to ring chromosome 20 [20]. …”

Emerging surgical therapies in the treatment of pediatric epilepsy

“…Deep brain stimulation has been used successfully for treatment of epilepsy in small series targeting the cerebellum (94), centromedian thalamic nucleus (95,96), and anterior nucleus of the thalamus (97)(98)(99). Targeting of the hippocampus, subthalamic nucleus, and caudate have also been reported (100)(101)(102)(103)(104)(105)(106)(107)(108). These early studies of openloop stimulation technology were important benchmarks in the use of neurostimulation to treat epilepsy and provided the foundation for RNS (109).…”

Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

“…In 2002, the Grenoble group reported 5 patients who underwent bilateral STN DBS (some with multiple leads) for inoperable seizures of various types [88,89]. Following their successful 2007 case report [85], Wille et al [90] reported a series of 5 adults with progressive myoclonic epilepsy who were implanted with STN DBS and followed in an unblinded fashion for 12-42 months.…”

“…Several small case series of STN stimulation have been reported [83][84][85][86][87][88][89]. In 2002, the Grenoble group reported 5 patients who underwent bilateral STN DBS (some with multiple leads) for inoperable seizures of various types [88,89].…”