Epilepsy surgery: just what is it?

In simple terms epilepsy surgery refers to surgery which is carried out to remove the area of the brain which is generating the seizures. Epilepsy surgery though needs careful planning and an extensive diagnostic work-up and hence is usually available only in level IV epilepsy centers. The epileptogenic focus (area of the brain generating the seizure) has to be identified and this is accomplished with the aid of video (continuous) EEG monitoring, at times intracranial EEG monitoring, MRI scans, PET and SPECT scans. Neuropsychological testing and a special test called WADA test is also done which helps to identify the location of language and memory centers in the brain.
After the above testing (some patients may need less, others additional testing), we determine whether a patient is a good surgical candidate, what kind of surgery to offer him and what are the chances that he shall be seizure free after epilepsy surgery.

Nitin K Sethi, MD

Devices in the treatment of epilepsy

Devices in the treatment of epilepsy

Nitin K Sethi, MD

A number of neurostimulation devices are now available for the treatment of medically refractory epilepsy. Medically refractory epilepsy is currently defined as the failure of the patient’s epilepsy to respond to the use of at least 2 frontline and appropriate anti-epileptic drugs (AEDs)) (some physicians use up to 3 drugs) used in a successive fashion.

Types of devices for the treatment of medically refractory epilepsy:

1. Vagus Nerve Stimulator (VNS)
2. Responsive Neurostimulator (RNS)
3. Deep brain stimulator (DBS)

Neurostimulation not a replacement for resective surgical options.

Vagus Nerve Stimulator (VNS): fundamental concepts

1. pacemaker like device to stimulate the Vagus (CN X) nerve.
2. manufactured by Cyberonics Inc, Houston, Tx
3. gained FDA approval in 1997 for the adjunctive treatment of patients over 12 years of age with medically intractable partial onset seizure disorder.
4. Approved in Europe in 1994.
5. simple device consisting of 2 electrodes, an externally programmable pulse generator and a battery pack.
6. the stimulating electrode is implanted around the midcervical portion of the left vagus nerve (composed of 80% afferent fibers) while the impulse generator along with the battery pack is implanted in a subcutaneous pocket in the left infraclavicular region.
7. left vagus nerve is the preferred site of stimulation due to the higher risks of cardiac arrhythmias with right vagus nerve stimulation as it innervates the sinoatrial node and thus influences heart rate and rhythm.
8. the pulse generator is programmed externally through the skin via a magnetic currently hand held wand.
9. different parameters of stimulation can be programmed such as current strength, pulse width, pulse train frequency, current on and off times as well as magnet current strength.
10. a magnet usually worn on the patient’s arm can provide on-demand stimulation.

Mechanism of action of VNS:

1. Not fully elucidated.
2. Vagus nerve has afferent inputs to multiple areas which may be involved in the generation or propagation of ictal activity: reticular formation, thalamus, cerebral cortex.
3. Electrical impulses via the left vagus nerve travel to the nucleus of tractus solitaries (NTS). From the NTS are outflow tracts to reticular formation and locus ceruleus (LC) increasing the release of norepinephrine and serotonin. VNS may thus increase the release of gamma amino butyric acid or inhibit the release of glutamate. Rats in which the LC is destroyed, VNS is no longer effective in controlling seizures.
4. Widespread cortical de-synchronization by the afferent volley of impulses leading to inhibition of recruitment of epileptic discharges may be another mechanism.
5. Alteration of cerebral blood flow (CBF) in specific areas of the brain-not widely accepted.
6. Peripheral stimulation of CN X may modify the epileptic network circuit in the brain by synaptic modulation.
7. Effects on the amygdala likely mediate the antidepressant effects and mood elevating effects of VNS.

Stimulation parameters which can be adjusted:

1. Output current (usual settings are between 1.5 and 2.25 mA)
2. Pulse width (usually between 250-500microsecs)
3. Frequency (usually between 20 to 30 Hz)
4. Time on (usually on for 30 secs)
5. Time off (usually off for 3 to 5 mins)
6. Magnet current (usually set at 0.25 mA above output current)
7. Fast cycling 7 secs on and 14 secs off.
8. Battery life depends upon stimulation settings

Generator models currently available:

1. 102 Pulse
2. 102 Pulse Duo
3. 103 Demipulse
4. 104 Demipulse Duo
5. 105 Aspire HC
6. 106 Aspire SR

Clinical efficacy of VNS:

1. Multiple studies establish the efficacy of VNS in patients with partial onset (focal) epilepsy both in children and adults.
2. Currently FDA approved for adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizures that are refractory to antiepileptic medications.
3. Currently FDA approved for the adjunctive long-term treatment of chronic or recurrent depression for patients 18 years of age or older who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments.
4. Used at times for generalized epilepsy but efficacy not established-lack of good quality studies.
5. Case reports showing efficacy in Lennox-Gastaut syndrome (LGS).

Side-effects/ complications of VNS therapy:

1. infection at the generator implantation site.
2. dyspnea, coughing bouts, laryngeal spasms and choking as current is increased.
3. dysphagia, odynophagia as current is increased
4. hoarseness or change in voice
5. thermal injury to the Vagus nerve can occur but is not commonly reported
6. use with caution in patients with COPD and asthma.
7. VNS may worsen pre-existing obstructive sleep apnea (OSA) due to central and peripheral mechanisms by altering the tone of the upper airways mucles.
8. Recommendation is to turn off VNS prior to CPAP titration.

Contraindications of VNS therapy:

1. MRI is not an absolute contraindication.
2. MRI can be carried out-but recommendation is to turn the device off first.
3. Interrogate device both before and after MRI scan.
4. Avoid use of short-wave diathermy, microwave diathermy and devices which generate strong electric or magnetic fields in the vicinity of the VNS.

Responsive Neurostimulation Device (RNS): fundamental concepts

1. Pacemaker like device to stimulate the epileptogenic focus or foci in the brain.
2. manufactured by NeuroPace, Mountain View, California.
3. generator is implanted in a pocket drilled into the skull bone by the neurosurgeon.
4. cortical strip leads and NeuroPace depth leads are implanted onto or into the epileptogenic focus or foci determined by
5. remote monitor and wand used by patient to interrogate device, collect data and upload to the Internet for the physician.
6. programmer and wand used by physician to collect data and program the neurostimulator.
7. a magnet can be swiped over the device to trigger storage of ECoG and also to temporarily stop stimulation.
8. FDA approved as adjunctive therapy in individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to two or more antiepileptic medications, and currently have frequent and disabling seizures (motor partial seizures, complex partial seizures and/or secondarily generalized seizures).
9. Unlike VNS which is an open-loop device, RNS is semi-closed. The device continuously records electrocorticogram (ECoG) and then based on an algorithm can be programmed to deliver brief pulses of electrical stimulation when it detects activity that could lead to a seizure.

Mechanism of action of RNS:

1. rationale for RNS is responsive stimulation of an epileptic focus/ foci in the brain
2. if stimulated in time and with current of appropriate intensity, evolving seizure shall get aborted
3. involves real time electrographic analysis and responsive and automatic delivery of stimulation

Stimulation parameters for RNS:

1. two different epileptogenic foci can be stimulated individually
2. wide range of stimulation settings/parameters that can be adjusted-from 40 to 1000 microseconds, 1 to 333 Hz, 0.5 to 12 mA

Clinical efficacy of RNS:

1. Results similar to other stimulation devices
2. At the end of 2 years, the median seizure reduction was 56%.

Side-effects/ complications of RNS therapy

1. Surgical complications during implantation of device-risk of hemorrhage, infection
2. Lead breakdown/disconnection
3. Replacement of generator requires another craniotomy
4. Patient needs close follow up for stimulation parameters adjustment hence not ideal for patients who live in rural areas or cannot come for regular follow ups.

Deep Brain Stimulator (DBS): fundamental concepts

1. Stimulation of the anterior nucleus of thalamus (ANT)
2. Electrodes implanted bilaterally in the ANT.
3. Stimulator and battery implanted under left clavicle.

Stimulation parameters for DBS:

1. high-frequency stimulation
2. 5 V, 145 pulses per sec, 90 microseconds, cycle time 1 minute on and 5 minutes off

Mechanism of action of DBS:

1. thalamus is a major relay station and thalamocortical networks are widely believed to be involved in seizure propogation by synchronization of ictal activity.
2. stimulation of ANT may cause desynchronization and thus inhibit seizure propogation.
3. in animal experiments low-frequency stimulation leads to EEG synchronization and high-frequency causes EEG desynchronization.

Clinical efficacy of DBS:

1. SANTE (stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy) study-results similar to other stimulation devices.
2. Fourteen patients were seizure-free for 6 months.

Side-effects/ complications of DBS therapy

1. Surgical complications during implantation of device-risk of hemorrhage, infection
2. Lead breakdown/disconnection
3. Replacement of generator requires another craniotomy
4. Patient needs close follow up for stimulation parameters adjustment hence not ideal for patients who live in rural areas or cannot come for regular follow ups.


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Analgesic overuse headache

Recently I saw a patient in the hospital who had complaint of constant severe daily headaches. She was a 34-year-old otherwise healthy African American woman who first developed headaches at the age of 15. At that time she used to get throbbing hemicranial (one half of the head) headaches which were accompanied by nausea. At times she used to throw up if the headache was particularly bad. During the headache episode she complained of light sensitivity (bright lights bothered her, we refer to this as photophobia) perferring to lie in a quiet dark room. Sleep usually aborted her headache attack. She was correctly diagnosed as suffering from common migraine (this is migraine which is not associated with aura) and treated with Inderal (propanolol-a beta blocker). Later she started using Imitrex (a triptan) whenever she had an acute migraine attack. Around the age of 18, she developed pelvic inflammatory disease for which she started using ibuprofen.

At the time of her current presentation, she said her headache character had changed. Now instead of having episodic migraine attacks, she had a headache “all the time”. She was taking 4-6 pills of ibuprofen a day and 8 to 10 Imitrex pills a month.

This brings us to the topic under discussion “analgesic overuse headaches” also at times referred to as “medication overuse headaches”. Research has shown that about 1% of the general population experiences medication overuse headache and the condition is thought to occur due to an interaction between a therapeutic agent (in this case an analgesic) used excessively by a suspectible patient.

The overuse of anti-migraine drugs and analgesics gives rise to a mixed picture of migraine-type and tension-type headaches that occur at least 15 days a month. Patients start taking more and more analgesics to treat the headache and this sets up a vicious cycle of headache-analgesic-headache-analgesic.

Chronic daily headaches due to overuse of analgesics are particularly difficut to treat. Analgesics are discontinued (some patients of course have worsening of their headache during this time). To keep headaches under check during this time (when the analgesics have been discontinued), the doctor may prescribe a low dose tricyclic antidepressant such as Elavil (amitriptyline). The headache usually resolves or reverts to its previous pattern within two months after discontinuation of the drug (analgesic).

Concussions-let us talk about it

Boxing picLately the topic of concussion is in the news again. Concussions are been increasingly recognized both on and off sports fields. A concussion may be defined as any traumatic brain injury (usually mild) that disrupts brain function. A point to emphasize here is that loss of consciousness is not mandatory for a concussion to occur. Let me explain this with the aid of an example from the sport of boxing. As a ringside physician I sometimes witness a knockout (KO). In a sudden dramatic KO the boxer falls to the canvas and is unable to rise to his feet before the count of 10. In most KOs it is easily apparent that the boxer has also suffered a concussion-he is rendered unconscious (sometimes only for a very short time) and when examined in the ring is frequently confused and disoriented (may not recall that he was knocked out, does not recall which round it is or the name of the arena). In these circumstances a concussion is easy to identify. There are though instances where the boxer may be struck by a ferocious blow such as a hook but he does not fall to the canvas nor does he suffer a loss of consciousness. In these circumstances the concussion is far harder to identify and many a times may be missed by the referee, the boxer’s own corner and even the ringside physician unless the fight is stopped temporarily and the boxer is assessed. Some people refer to these as sub-concussive injuries/blows.

Current scientific data indicates that multiple concussions are not good for the brain and there is concern (some degree of evidence but not definite proof) that it leads to a progressive degenerative disease of the brain called chronic traumatic encephalopathy (CTE) for which currently there is no cure. As prevention is always better than cure, hence the thrust that concussions especially on the sports field be identified in a timely and accurate fashion and athletes be rested (removed from play) till they are asymptomatic.

Nitin K Sethi, MD

The Poor Me Syndrome-Social media networking sites like Facebook and their adverse neurological and psychiatric consequences

The Poor Me Syndrome-Social media networking sites like Facebook and their adverse neurological and psychiatric consequences

Nitin K Sethi, Prahlad K Sethi

The spread and reach of the Internet has heralded a social media revolution in its wake. Social media are a group of Internet-based applications (networking websites, blogs, microblogs, content communities, virtual game worlds) that allow creation and exchange of user-generated content. The use of social media networking websites like Facebook, Twitter and LinkedIn has increased exponentially. In 2014 the total number of monthly active Facebook users was reported to be 1,310,000,000 and total number of minutes spent on Facebook per month was 640,000,000. Forty eight percent of Facebook users log in every day and an equal percentage of users between the ages of 18-34 reportedly check Facebook on waking up. 1We are today more connected to each other than ever before. How we communicate with each other, exchange and share information has undergone a pervasive change. Gone are the days when one kept in touch with family and a few close friends either via postal mail (nowadays referred to as snail mail or smail-yes smail was slow but dependable) or via the invention of Alexander Graham Bell (collect call anyone?). Today’s generation has e-mail, cellphones and cellphone apps. We prefer to text rather than call someone in person, e-mail rather than put pen to paper.

A year ago a 28-year-old young lady consulted me for her seizure disorder. At the time of her presentation; she was on 4 anticonvulsant medications, seizures were well controlled but she was experiencing cognitive side-effects and fatigue. Over the ensuing months under close observation, I began to taper her off one anticonvulsant. Her seizure control remained stable and she felt better. All was going well till one day I received a frantic call from her mother. My patient had attempted suicide by overdosing on her anticonvulsants. She was rushed to a local hospital and later transferred to my hospital where she remained in the intensive care unit for 10 days. As her condition stabilized, she was transferred to the neurology floor and later discharged to a rehab facility. I had the opportunity to speak to her mother recently and asked her the reason why her daughter had attempted suicide. Her attempted suicide it turned out was neither related to her seizure disorder nor her anticonvulsants. Rather she fell a victim to the poor me syndrome. Two of her friends on Facebook had changed their status from single to married and one had uploaded pictures frolicking in the sun with her new beau. Seeing those updates had made my patient feel that life as it was for her was not worth living.

The poor me syndrome is likely an under recognized and under reported consequence of social media networking sites like Facebook. We are increasingly conscious about our online persona and how we reflect that to others. So happy memories and status changes are more likely to be uploaded and updated than times of sadness and struggle. In the days of yore before Facebook was born we knew little what our friends were up to in their lives- who were getting married, who had a new girlfriend or had purchased an awesome house by the beach. Ignorance as they say is indeed bliss for what we did not know did not affect us. Now though; a happy post by one of your friend risks creating sadness and feelings of hopelessness in you.


1. Facebook statistics. http://www.statisticbrain.com/facebook-statistics/2014.