Neuromodulation in Epilepsy. Gregory C. Mathews, M.D., Ph.D.

Transcription

1 Neuromodulation in Epilepsy Gregory C. Mathews, M.D., Ph.D.

2 Disclosure There are no disclosures to share with regards to this presentation.

3 Epilepsy Basics What is epilepsy? Partial versus generalized Treatment of epilepsy Refractory epilepsy

4 Epilepsy What is epilepsy? A chronic disorder characterized by recurrent (at least two) unprovoked seizures What is a seizure? The manifestations (symptoms and signs) of excessive and hypersynchronous, usually self limited, activity of networks of neurons in the brain

5 Not Only a Pediatric Disease

6 Prevalence and Causes Prevalence in most developed countries is 4 to 10 per 1000 people ( = 1% of the population)

7 Physiology of a Seizure

8 Electroencephalography

9 Epilepsy Classification: Partial epilepsy

10 Epilepsy Classification: Primary generalized epilepsy

11 Seizure Focus and Spread thalamus

12 Treatment of Epilepsy Complete seizure remission is the main determinant of quality of life Medication is the mainstay of treatment In newly diagnosed patients: 1/2 are seizure free on first medication 2/3 eventually become seizure free More than 20 medications are available Most modulate excitability by decreasing neuronal excitation or enhancing neuronal inhibition

13 Limitations of Antiepileptic Medications Control seizures, do not cure or change long term prognosis Many patients have adverse effects Drowsiness, dizziness Cognitive Long term eg. bone metabolism Teratogenicity Adherence is difficult, non-adherence is dangerous

14 Refractory Epilepsy 30-40% of people with epilepsy do not have good control with medications In some people, drug resistance develops In some people, the underlying disease is different or changes over time Seizure free for the past year Generalized 82% Post-stroke 54% Dysgenetic 24% Hippocampal atrophy 10% Dual pathology 3%

15 Treatment options when patients are medically refractory Resective surgery Ketogenic diet Vagus nerve stimulator Newer stimulation technologies

16 Resective Surgery: The Only Cure Identify the seizure focus and resect it

17 Surgical treatment of temporal lobe epilepsy

18 Resective Surgery: Not for everyone! Easy decision Lesion (eg. tumor, developmental anomaly, vascular malformation) Hippocampal sclerosis More difficult decision Partial epilepsy with no structural abnormality Not an option Generalized epilepsy Seizure focus involves eloquent cortex Multiple seizure foci

19 Electrical stimulation for seizure cessation

20 Vagus nerve stimulation

21 Anatomy of Vagus Nerve From: GI Motility online (2006)

22 Central nervous system influence of vagus nerve From Journal of Cerebral Blood Flow & Metabolism

23 Vagus nerve stimulation: a long history 1950 s, vagus nerve stimulation shown to produce desynchronization of the EEG in animal models 1980 s: VNS shown to prevent seizures in animal models 1990 s: VNS tested in humans with epilepsy 1997: VNS approved for use in patients with refractory partial-onset seizures

24 What is the VNS? The VNS Therapy System consists of an implanted pacemaker-like generator and nerve stimulation electrodes, which deliver intermittent stimulation to the patient s left vagus nerve that sends signals to the brain

25 Therapeutic stimulation parameters Parameters Units Range Typical Output current Milliamps (ma) Signal frequency Hertz (Hz) Pulse width Microseconds (µsec) Signal ON time Seconds (sec) Signal OFF time Minutes (min)

26 Results of VNS Therapy 60% % of Patients with 50 seizure frequency reduction 50% 40% 30% 20% 10% 0% 3 months 1 year 2 years 3 years Morris GL, et al. Neurology 1999;53:

27 VNS Side Effects Hoarseness Cough Paresthesia Shortness of breath Notably ABSENT side effects: Medication adverse effects Eg. sedation or dizziness, cognitive effects, drug interactions, bone loss, teratogenicity

28 Who should try VNS? Patients who: Are refractory to medications Experience severe medication side effects Are not candidates for resective surgery

29 Responsive Stimulation

30 A closed loop system monitors EEG and detects seizure onset delivers electrical impulse to site of seizure origination requires identification of the focus and programming to set parameters for detection and impulse delivery What is RNS?

31 Results with RNS Approximately 30% reduction in seizure frequency 191 patients 1 or 2 seizure foci Morrell MJ: Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 77: , 2011

32 Deep Brain Stimulation

33 DBS for epilepsy 1960 s 1970 s: recognized that lesions of the anterior thalamus could reduce seizure frequency in animal models and in humans

34 SANTE Trial

35 Results with DBS

36 Summary of Stimulation for Epilepsy Table 1. Large randomized controlled trials of brain stimulation Authors & Year No. of Patients Target Seizure Frequency Reduction Group Treatment Sham Ben-Menachem et al., VNS 25% 6% Handforth et al., VNS 28% 15% Fisher et al., ANT 40.4% 14.5% (median) Morrell et al., direct-seizure foci 37.9% 17.3%