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Доклад Др МакКормика

Доклад Др МакКормика

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Доклада ведущего детского нейрохирурга King's College Hospital доктора Дэвида МакКормика посвящен проблеме нейрореабилитации после перенесенной мозговой травмы.
Доклада ведущего детского нейрохирурга King's College Hospital доктора Дэвида МакКормика посвящен проблеме нейрореабилитации после перенесенной мозговой травмы.

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Vagus Nerve Stimulation for the treatment of Refractory Childhood Epilepsy

Dr David McCormick Consultant Paediatrician, Neurorehabilitation & Epilepsy

Seizure freedom with AEDs
• After adequate trials of at least 2 AEDs, overall response rates with subsequent treatment trials are dramatically decreased

35% 50%

Seizure Free with First Drug Seizure Free with Second Drug

Seizure Free with Third Drug or multiple drugs
Refractory Population





Mohanraj R and Brodie MJ. Eur J Neurol. 2006;13:277-282.


Non-drug treatments for patients refractory to AEDs

Non-AED treatments should be considered in patients refractory to medication The definition of „refractory‟ needs to be considered carefully – after 2 appropriate AEDs, when adding a further AED seizure freedom is unlikely and a significant reduction in seizures will occur in only a minority Non-AED treatments include epilepsy surgery, the Ketogenic Diet (KD) and Vagus Nerve Stimulation (VNS) Epilepsy surgery should always be excluded as a possibility before VNS is considered

Vagus Nerve Stimulation

VNS Therapy is the implantation of a medical neurosimulator device
VNS delivers intermittent electrical stimulation to the left cervical vagus nerve Why the cervical vagus nerve? Afferent pathway to the brain: 80% afferent fibers Projects to areas responsible for seizures, mood, appetite, memory and anxiety Easy access Few pain fibers Left vagus has less cardiac innervation than right

VNS Therapy European Indication for Use

“...indicated for use as an adjunctive therapy in reducing the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures (with or without secondary generalization) or generalized seizures, which are pharmacoresistant to antiepileptic medications.”

Physician’s Manual.

When to consider VNS

Wheless JW. Neurostimulation Therapy for Epilepsy. In: Wheless JW, Willmore LJ, Brumback RA, eds. Advanced Therapy in Epilepsy. Hamilton, Ontario: BC Decker, Inc.

VNS: mechanism of action
VNS Therapy

Neurotransmitter Expression

Cerebral Blood Flow  Thalamus8,11  Cortex8,11

Changes in EEG Desynchronization EEG rhythms9,10

 Norepinephrine1,2,7  GABA3,5,6  Serotonin4,5  Aspartate4,5

Anti-convulsive effect
1. Roosevelt RW, et al. Brain Res 2006;1119(1):124-32. 2. Hassert DL, et al. Behavioral Neuroscience 2004;118(1):79-88. 3. Woodbury DM and Woodbury JW. Epilepsia 1990;31 (Suppl. 2):S7-S19. 4. Hammond BM, et al. Brain Research 1992;583:300-3. 5. Ben-Menachem E, et al. Epilepsy Res 1995;20:221-7. 6. Marrosu F, et al. Epilepsy Res 2003;55:59-70. 7. Krahl S, et al. Epilepsia. 1998;39:709-714. 8. Henry TR, et al. Epilepsia. 2004;45(9):1064-1070. 9. Wang H et al., J Neurosci. 2009 ;in press. 10. Koo B. J Clin Neurophysiol. 2001;18:434-441. 11.Vonck K, et al. Seizure 2008; 17(8):699-706



VNS Therapy Implant Procedure

Approximately 1 hour

General or regional/local anaesthesia
Chest/axillary border incision for pulse generator Neck incision for lead Day case or inpatient Neuro surgeon or ENT surgeons

VNS surgical procedure

VNS Surgical Procedure

Anchor Tether  Caudal Positive Electrode

Cephalad 
Negative Electrode

VNS Therapy
Surgical Complications

Clinical Studies (N=454)1 Infection without explant Infection with explant Hoarseness/temporary vocal cord paralysis Hypesthesia/lower left facial paresis All Patients (N=15,000+) Asystole during routine lead test Mortality 0.1% 0.0% 1.8% 1.1% 0.7% 0.7%


et al. Epilepsia.1998;39(Suppl 6):92-93.

VNS Therapy: Efficacy

% of Patients with 50 seizure frequency reduction

64% 57% 50% 51% 59%

MeanF/U 33 mo 12

MeanF/U 3 mo

MeanF/U 12 mo

MeanF/U 44 mo

MeanF/U 59 mo

1. Vonck K, et al. J Clin Neurophysiol 2004;21:283-9. 2. Renfroe JB and Wheless JW. Neurology 2002;59(suppl 4):S26-S30. 3. Labar DR. Seizure EUSym12-11-1002-EEA 2004;13:392-8. 4. De Herdt V, et al. Eur J Paediatr Neurol 2007;11:261-9. 5. Elliott RE, et al. Epilepsy Behav 2011;20(1):57-63.

Vagus nerve stimulation in 436 consecutive patients with treatmentresistant epilepsy: Long-term outcomes and predictors of response
Elliott RE, et al. Epilepsy & Behavior 20: 57-63, 2011



Patient characteristics
Females Males Mean age at seizure onset Mean duration of epilepsy prior to VNS Mean age at VNS insertion Adults (≥18 years) Children <18 years Children ≤12 years Median seizure frequency (per week)

No. (%) or mean ± SD (range)
220 (50.5%) 216 (59.5%) 9.4 years ± 11.5 (birth–59 years) 19.2 years ± 13.0 (8 mos–66 years) 29.0 years ± 16.5 (1.3-76) 307 (70.4%) 129 (29.6%) 86(19.7%) 4 (0.1–2000)

Mean number of AEDs at baseline
Mean number of AEDs failed Prior failed intracranial epilepsy surgery Number of seizure types Developmental delay

2.7 (0–7)
5.6 (1–19) 127 (29.1%) 2.0±1.0 (1–6) 221 (56.4%)

Elliott RE, et al. Epilepsy & Behavior 20: 57-63, 2011

Responder rates

% of Patients



n =162


Elliott RE, et al. Epilepsy & Behavior 20: 57-63, 2011

Results overview

• Predictors of seizure control with VNS Therapy?
– Focal EEG findings predicted improved seizure control (n=46, P=0.004) – Trend for patients exhibiting exclusively focal seizures to having better seizure control (P=0.09)

• No difference in percentage seizure reduction between
– Adults and Children – Patients who failed Intracranial Epilepsy Surgery (IES) and those who had pre-surgical multidisciplinary conference recommendations of IES over VNS

Elliott RE, et al. Epilepsy & Behavior 20: 57-63, 2011


Quality of Life with VNS Therapy
Recent Publications

Quality-of-life improvements
Promotes alertness1 Reduces daytime sleepiness1 Improves mood2 Improves memory3 Global improvement in quality of life4

Patient satisfaction reflected by long-term retention rates
59% at King‟s College Hospital


BA. et al. Neurology. 2001;57:879-884. CL, et al. Epilepsy Behav. 2000;1:93-99. 3Clark KB, et al. Nature Neurosci. 1999;2:94-98. 4Dodrill C, Morris GL. Epilepsy Behav. 2001;2:46-63.

Vagus Nerve Stimulation for Refractory epilepsy in Children - Conclusions

A valuable additional non-pharmacological treatment for children with refractory epilepsy with responder rates of 44%64% even in this refractory group Well tolerated treatment with high retention rate (eg 57%) in children Evidence of a positive impact of VNS on QoL for some children (and ?their carers), some of this independent of seizure effect and inclusive of improved behaviour/alertness in some Provisional data suggesting that early implantation may afford better outcome for seizure control than late implantation Larger studies are needed to clarify the early vs late question and offer more information on specific seizure types or syndromes

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