Concussions and the risk of post-traumatic epilepsy

Concussions and the risk of post-traumatic epilepsy

 

A concussion is a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces. Immediately following a concussion, an athlete is usually advised physical and cognitive rest till post-concussion symptoms abate. The athlete then enters a stepwise return to play protocol. Premature return to play risks a second concussion, second impact syndrome, exacerbation and persistence of post-concussive symptoms.

 

Sports and Epilepsy

Sport is important not only in normal healthy populations, but also in persons with medical illness, physical or mental disabilities. Active participation in sports is beneficial physically and psychologically. The main concern in sports for persons with epilepsy is safety.

 

Why are people with epilepsy restricted from some sports?

 

Rationale is that the occurrence of an untimely seizure during certain sporting event has the potential for causing substantial injury and bodily harm both to the patient with epilepsy as well as fellow athletes and even spectators.

 

Example: if a person with epilepsy has a generalized convulsion or a complex partial seizure while skydiving: he shall not be able to deploy his parachute and a fatal accident can occur.

 

:a person with epilepsy taking part in an automobile racing event suffers a seizure while making a bend at speeds in excess of 100mph

 

:a person with epilepsy suffers a seizure while taking part in a swimming meet.

 

:a person with epilepsy suffers a seizure while bicycling

 

:a person with epilepsy suffers a seizure while horseback riding

 

:a person with epilepsy suffers a seizure while skiing down a steep hill

 

:even things more mundane such as having a seizure while running on a treadmill, while playing tennis, while jogging outside have the potential to cause bodily harm to the patient and others.

 

 

Why are people with epilepsy restricted from some sports?

 

Rationale is that repeated injury to the head (concussions) during some sports could potentially exacerbate seizures.

Example: a person with epilepsy who is indulging in contact sports such as boxing, karate, kick-boxing, muay thai boxing, American football, ice-hockey, wrestling, judo

 

But are these restrictions and fears actually based on scientific evidence or are they unfounded? Which sports are safe and which are not? Could indulgence in some sports make seizures potentially worse Vs. could some sports actually be beneficial for people with epilepsy (physically and psychologically)? Can vigorous physical exercise provoke seizures?

 

 

Exercise and seizures

 

One reason that people with epilepsy have been traditionally restricted from certain sports is the fear both in the patient and the treating physician that exercise especially aerobic exercise may exacerbate seizures. Some studies have shown an increase in interictal discharges during or after exercise. Most frequently these patients have generalized epilepsies. At least some frontal lobe and temporal lobe seizures are clearly precipitated or at times solely occur during exercise suggests that these are a form of reflex epilepsies. A number of physiologic mechanism by which seizures may be provoked by exercise have been postulated. These include hyperventilation with resultant hypocarbia and alkalosis induced by exercise. Another possible mechanism which is postulated to cause exercise induced seizures is hypoglycemia. This usually causes seizures after exercise in diabetic patients. Other mechanisms which have been postulated for exercise triggered seizures include the physical and psychological stress of competitive sports and potential changes in anti-epileptic drug metabolism. Exercise is a complex behavior and involves not such the motor system and the motor cortex but also involves other domains such as attention, concentration, vigilance and presumably some limbic networks which mediate motivation, aggression and competitiveness. Hence it is possible that patients who have temporal or frontal lobe epilepsy may on rare occasions have seizures triggered by exercise.

 

There is some limited evidence that exercise may in fact be protective and have physical, physiological and psychological benefits in patients with epilepsy. Electroencephalographic studies have shown that inter-ictal epileptiform discharges either remain unchanged or may decrease during exercise so there is some hint that exercise may actually raise the seizure threshold. Regular exercise also influences neuronal and hippocampal plasticity by upregulation of neurotropic factors. There is further evidence to suggest that regular physical exercise can improve the quality of life, reduce anxiety and depression and improve seizure control in patients with chronic epilepsy.

 

 

 

 

 

 

 

 

What sports are off limits for people with epilepsy?

 

No sport is completely off limit for a patient with epilepsy. Key though is proper supervision to reduce the potential for injury. There are some sports such as skydiving, automobile racing, swimming in the open seas and horseback riding which should be avoided by patients with epilepsy. Other sports can be enjoyed by patients with epilepsy but one should remember that they all have the potential to result in bodily harm if seizures occur when the patient is not supervised or if he is not wearing protective head and body gear.

 

 

Concussion and seizures (post traumatic epilepsy): what is the link?

 

The link between concussion (closed head trauma) and seizures has been and continues to be closely looked at. The fear of concussions (minor head trauma) making seizures worse is the prime reason why people with epilepsy are discouraged from some sports such as tackle football, ice-hockey, boxing, mixed martial arts and wrestling. The human skull is quite resilient and the closed head trauma has to be significant for it to result in seizures. Usually a concussion which results in prolonged loss of consciousness (some authors say more than 30 minutes) is graded as a significant head trauma. Minor bumps and bruises to the head do not cause seizures, do not increase the risk of future seizures and more importantly do not make chronic epilepsy worse. Seizures may occur immediately following a severe closed head trauma. Immediate post traumatic seizures by definition occur within 24 hours of the injury. They have also been referred to as impact seizures. Early post traumatic epilepsy refers to seizures which occur about a week to 6 months after the injury. Seizures may occur as far out at 2 to 5 years after head trauma (late post traumatic epilepsy). Factors which increase the risk of post traumatic seizures/ epilepsy include severity of trauma, prolonged loss of consciousness (more than 24 hours), penetrating head injury, intra or extraaxial hemorrhage, depressed skull fracture and early post traumatic seizures.

Counseling patients

 

Patients with epilepsy should be encouraged to exercise and take part in sports. My personal feeling is that no sport should be off limits to them with the exception of maybe sky-diving, river rafting and boxing. The goal should be exercising and playing sports safely. Walking, running, cycling and yoga are great exercises which can be indulged in with little to no risks. I advise all my patients with epilepsy (especially those with poorly controlled epilepsy) to wear a Medic Alert bracelet or carry a card in their wallet. This is of immense help were a seizure to occur in the field (as for example when a patient is jogging or cycling and is not in the immediate vicinity of his or her home). Low risk recreational sports such as walking or running usually do not need a one is to one supervision if seizures are well controlled by history. Team sports such as volleyball, basketball, baseball and softball are popular sports which carry a low risk of injury. For cycling I advise my patients to wear a helmet and have their bikes fitted with lights and reflectors. I also advise them to keep off from the busy city streets. “you do not want to have a seizure at the wrong place and at the wrong time”. Swimming is a great way to keep fit and also to meet and make friends. I feel many patients with epilepsy are discouraged from swimming due to an irrational fear of caregivers and physicians of drowning. I advise my patients not to swim alone. Most of the city pools have life guards and a polite request to them to keep a watch out goes a long way in reassuring both the patient and the caregivers. Swimming in the open seas is more risky. I advise my patients to swim close to the beach under the watchful eyes of a life guard. Also having a buddy around helps, preferably someone strong enough to pull the patient out of the water if a seizure was to occur. The option of wearing a life jacket is under utilized.

 

Final thoughts (a patient’s perspective)

 

These are the thoughts of a young patient of mine:

 

“I have always been a very active person and love playing sports such as Tennis, Yoga, Running etc, and I always try to pursue my dreams and not let things get in the way, but being epileptic, it is sometime hard to not worry about things happening. Whenever I play sports I get hot easily (face turns purple) and in the back of my head I find myself always hoping that nothing happens that would cause me to have a seizure. I ran my first half marathon two years ago, and in the back of my head there is always the thought of something happening, so I started to motivate myself by saying “I can do this, you will be fine.” My father taught me when I was younger that I can choose to let it hold me back or make the most of life! Many people consider epilepsy a disability, but I try not to because I don’t let it hold me back.”

 

 

Nitin K Sethi, MD, MBBS, FAAN Assistant Professor of Neurology New York-Presbyterian Hospital Weill Cornell Medical Center

Insomnia-what we know and how to treat it

Insomnia-what we know and how to treat it

 

 

Nitin K Sethi, MD, MBBS, DNB (Int Med), FAAN

 

 

 

 

In this blog post I shall address insomnia. Insomnia is a rather common medical problem for which patients consult doctors and sleep physicians. Broadly speaking insomnia can be of two types: sleep onset insomnia (the person finds it hard to fall asleep. Normal sleep latency is usually around 10 to 15 mins. Patients with sleep onset insomnia lie in bed sometimes for hours but sleep eludes them) and sleep maintenance insomnia (normally humans should be able to maintain sleep for 6 to 8 hours, though some of us are short sleepers and others long sleepers. People with sleep maintenance insomnia are unable to maintain sleep waking up multiple times during the night and struggling to fall back asleep again). One of the most common type of insomnia is psychophysiological insomnia and this is what I shall address in detail.

 

Psychophysiological insomnia (PPI)-these are people who cannot “shut their brains down at night”. At night when they settle down to sleep, their mind races (they are thinking about various things-work, personal issues and so forth). As a result they cannot sleep and keep looking at the clock. Over time this behavior gets reinforced to the extent that sleep itself becomes an anxiety provoking stimulus. Meaning they are anxious at night. Most of the people who suffer from PPI also suffer from anxiety and depressive disorders.

 

How to diagnose psychophysiological insomnia-usually a good history is sufficient in helping to diagnose PPI. Do you think a lot when you are lying in bed? Do you find it difficult to shut/power your brain down? Do you feel anxious in your own bed? Do you suffer from anxiety disorder and depression? Are your insomnia problems chronic (lasted more than 6 months)? Were other causes of insomnia ruled out such as insomnia due to medical problems (congestive heart failure, COPD, nocturnal asthma), insomnia due to certain medications and so forth. Your doctor may order a sleep study. The sleep study is done to rule out obstructive sleep apnea as a cause of disturbed sleep. It also helps your doctor get an idea of your sleep architecture (how much time you spent in different stages of sleep-light Vs. deep Vs. REM). Your doctor may also ask you to maintain a sleep diary. This is a record of your sleeping habits for a period of usually 2 weeks and helps the doctor better understand your sleep quality and hygiene.

 

Treatment of psychophysiological insomnia-treatment of PPI can be extremely challenging for the physician and frustrating for the patient. There is no good treatment but let us talk about what is out there, what helps and what does not.

  1. Cognitive behavioral therapy (CBT-I) for insomnia is probably what works the best. CBT-I is usually administered by a psychologist and involves several sessions spread over weeks. The therapist attempts to figure out what thoughts keep the patient awake at night and addresses them. Instructions to help structure sleep and wake up times is an important component of CBT-I. CBT-I takes time to act but in the long term is probably equally if not more effective and safer for treatment of PPI than sleeping pills (sedative-hypnotic medications).
  2. Sedative-hypnotic medications (sleeping pills)-there are numerous on the market both over the counter (OTC) ones such as Benadryl, Zzz Quil (to name a few) and prescription ones such as Ambien, Lunesta, Sonata, Belsomra, clonazepam, diazepam, Xanax (to name a few). These medications do work and they work by increasing chemicals in brain that promote sleep namely GABA. Belsomra is a new drug which was launched recently. As compared to other drugs, it works by decreasing chemicals in the brain that keep us awake. Sleeping pills have the advantage that they work quickly but they have 2 big problems. Regular/nightly use of sleeping pills makes the patient dependent upon them. The other problem with regular/nightly use is tolerance (example initially 5 mg of Ambien works great but then it stops acting and the patient needs a higher dose of Ambien say 10 mg to achieve sleep).
  3. Sedating anxiolytic-antidepressant medications: examples include Trazodone, Doxepin and amitriptyline. These medications are taking on a nightly basis and the goal is to address PPI by treating the patient’s anxiety disorder. The sedating qualities of these medications initially is useful in helping patient’s fall asleep.
  4. Non-sedating anxiolytic-antidepressants medications: examples include Paxil and Celexa to name a few. Goal here is to treat the patient’s anxiety/depression. Since these are not sedating, they are administered during the day.
  5. Entraining the circadian rhythm: one important thing which is ignored when insomnia is treated is entrainment of the patient’s circadian rhythm. In the hypothalamus of the brain there are a group of brain cells (called suprachiasmatic nucleus) which helps to maintain circadian rhythm (sleep wake cycle). Many patients with insomnia have poorly entrained circadian rhythm with no regular sleep-wake times. They are frequently night owls and so when they get into bed early say around 11 pm, they are unable to fall asleep since the sleep drive is not there (their brain may be geared to fall asleep around 1 pm). So it is important to structure sleep with the establishment of regular sleep wake times. The circadian rhythm is entrained by light and exercise. Patients should be encouraged to expose themselves to sunlight in the morning after waking up. Exercise in the morning is also helpful.
  6. Steps to improve sleep hygiene: Use the bed only for sleeping or sex. Do not carry your work to bed. Do not use laptops, smart phone while in bed. Your brain should associate your bed with sleep and not work. Half an hour before bedtime, room lights should be dimmed. TV, computers and smart phones should be tuned off and one should engage in activities that relax and calm the brain. This may be reading a book, meditating or even watching TV if that relaxes you. A hot shower before bedtime, drinking hot decaffeinated tea or warm milk increases the core body temperature and promotes good sleep. Deep slow breathing exercises are also very helpful (you can find some of these on the Internet).

I hope you find this blog posting on sleep and insomnia helpful. Sweet dreams everyone!

Mirror mirror on the wall who is the smartest doctor of them all?

Mirror mirror on the wall who is the smartest doctor of them all?

Nitin K Sethi, MD

New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, U.S.A.

As a resident in training, I quickly came to the realization that some of my attendings were smarter than others. No matter how vexing the clinical problem these were the few who always knew the answers. I would present the history, examination findings and pertinent labs and voila these master clinicians would be able to put the pieces of the puzzle together. If they did not know the answer right away, they always knew where and how to look for it. What organ system to focus on and what tests to order. They stood out in stark contrast to my other attending, all ‘good’ neurologists but who I frequently found ordering multiple and at times random tests struggling to find answers to what plagued the patient. Eccentric with bedside manners that at times bordered on the theatrical, these master clinicians on the other hand made medicine fun and easy. It was as if they could walk into a patient’s room and smell his disease.
I frequently wondered what set these doctors apart from others. It could not be the medical school or the residency program they graduated from. Few were from Ivy League colleges and a seldom few were known outside the corridors of the institution they served in. On the other hand a good number of the ‘good’ doctors made it to the New York’s best doctors list time and time again. Was it their depth of knowledge? Many of the ‘good’ doctors would quote articles and studies with ease but still came up short at the patient’s bedside. It had to be Factor E (excellence factor) coded by the M (master) gene. Only a chosen few had it.

Now when I am on the other side of the fence teaching residents and fellows in training, I still at times wonder whether master clinicians are born de novo (with copious amounts of Factor E) or whether a chosen few good physicians become master physicians and the rest remain good. A lot has been written about improving residency training. The goal is to produce competent physicians at the end of the training process but can good residents be trained to become master clinicians? Is Factor E teachable and transferable? Does training under the wings of these masters automatically ensure transfer of gene M to the trainee? The field of medicine glitters with examples of master clinicians who taught, mentored and inspired their residents and fellows to become master clinicians themselves. A closer look at these attending teacher-resident trainee relationships is worthy of our attention. The patient’s bedside is your laboratory is the central tenant that master clinicians teach their students encouraging them to spend time at the patient’s bedside hearing their stories with rapt attention for a small detail in the patient’s history may very well be the key which unlocks the whole puzzle. Sherlock Holmes the master sleuth once told his prodigy Dr. Watson “you see but you do not observe”. Blessed with astute powers of observation and an analytical mind master clinicians similarly teach their students that the eyes do not see what the mind does not know. James Parkinson, a master clinician in his own right, in his short monograph titled “The Shaking Palsy” described 6 patients in total, three of whom he simply observed walking on the city streets. Much of the description of the longitudinal course of the illness we now know as Parkinson’s disease was derived from his observations of a single case only. Master clinicians report just not their successes but also their failures. Always remembering and learning from their failures constantly striving to become better they inspire trainees to follow in their footsteps. Knowing all too well that medicine never was nor shall ever be an exact science, they encourage their trainees not to hesitate to think out of the box when confronted with a vexing case. “When you have eliminated the impossible, whatever remains, however improbable, must be the truth” another quote attributed to Sherlock Holmes is well worth remembering. Last but not the least these lone stars of neurology teach their trainees the importance of treating patients with respect and dignity reminding them ever so gently that our patients remain our best teachers.

“He who studies medicine without books sails an uncharted sea, but he who studies medicine without patients does not go to sea at all.”
(William Osler-Canadian physician 1849-1919)

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.


References

1. Parakh M, Katewa V. Non-pharmacologic management of epilepsy. Indian J Pediatr. 2014 Oct;81(10):1073-80. doi: 10.1007/s12098-014-1519-z. Epub 2014 Jul 5.
2. Ulate-Campos A, Cean-Cabrera L, Petanas-Argemi J, García-Fructuoso G, Aparicio J, López-Sala A, Palacio-Navarro A, Mas MJ, Muchart J, Rebollo M, Sanmartí FX. Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life. Neurologia. 2014 Jun 26. pii: S0213-4853(14)00122-4.
3. Terra VC, Amorim R, Silvado C, Oliveira AJ, Jorge CL, Faveret E, Ragazzo P, De Paola L. Vagus nerve stimulator in patients with epilepsy: indications and recommendations for use. Arq Neuropsiquiatr. 2013 Nov;71(11):902-6.
4. Meneses MS, Rocha SF, Simão C, Santos HN, Pereira C, Kowacs PA. Vagus nerve stimulation may be a sound therapeutic option in the treatment of refractory epilepsy. Arq Neuropsiquiatr. 2013 Jan;71(1):25-30.
5. Wang DD, Deans AE, Barkovich AJ, Tihan T, Barbaro NM, Garcia PA, Chang EF. Transmantle sign in focal cortical dysplasia: a unique radiological entity with excellent prognosis for seizure control. J Neurosurg. 2013 Feb;118(2):337-44.
6. Spatola M, Jeannet PY, Pollo C, Wider C, Labrum R, Rossetti AO. Effect of vagus nerve stimulation in an adult patient with Dravet syndrome: contribution to sudden unexpected death in epilepsy risk reduction?. Eur Neurol. 2013;69(2):119-21.
7. Aron M, Vlachos-Mayer H, Dorion D. Vocal cord adduction causing obstructive sleep apnea from vagal nerve stimulation: case report. J Pediatr. 2012 May;160(5):868-70.
8. Elliott RE, Morsi A, Kalhorn SP, Marcus J, Sellin J, Kang M, Silverberg A, Rivera E, Geller E, Carlson C, Devinsky O, Doyle WK. Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav. 2011 Jan;20(1):57-63.
9. Ashton AK. Depressive relapse after vagal nerve stimulator explantation. Am J Psychiatry. 2010 Jun;167(6):719-20.
10. Air EL, Ghomri YM, Tyagi R, Grande AW, Crone K, Mangano FT. Management of vagal nerve stimulator infections: do they need to be removed? J Neurosurg Pediatr. 2009 Jan;3(1):73-8.
11. Bergey GK, Morrell MJ, Mizrahi EM, Goldman A, King-Stephens D, Nair D, Srinivasan S, Jobst B, Gross RE, Shields DC, Barkley G, Salanova V, Olejniczak P, Cole A, Cash SS, Noe K, Wharen R, Worrell G, Murro AM, Edwards J, Duchowny M, Spencer D, Smith M, Geller E, Gwinn R, Skidmore C, Eisenschenk S, Berg M, Heck C, Van Ness P, Fountain N, Rutecki P, Massey A, O’Donovan C, Labar D, Duckrow RB, Hirsch LJ, Courtney T, Sun FT, Seale CG. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. 2015 Feb 24;84(8):810-7
12. Cox JH, Seri S, Cavanna AE. Clinical utility of implantable neurostimulation devices as adjunctive treatment of uncontrolled seizures. Neuropsychiatr Dis Treat. 2014 Nov 14;10:2191-200.
13. Morrell MJ. In response: The RNS System multicenter randomized double-blinded controlled trial of responsive cortical stimulation for adjunctive treatment of intractable partial epilepsy: knowledge and insights gained. Epilepsia. 2014 Sep;55(9):1470-1.
14. Heck CN, King-Stephens D, Massey AD, Nair DR, Jobst BC, Barkley GL, Salanova V, Cole AJ, Smith MC, Gwinn RP, Skidmore C, Van Ness PC, Bergey GK, Park YD, Miller I, Geller E, Rutecki PA, Zimmerman R, Spencer DC, Goldman A, Edwards JC, Leiphart JW, Wharen RE, Fessler J, Fountain NB, Worrell GA, Gross RE, Eisenschenk S, Duckrow RB, Hirsch LJ, Bazil C, O’Donovan CA, Sun FT, Courtney TA, Seale CG, Morrell MJ. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia. 2014 Mar;55(3):432-41.
15. Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Tröster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25.