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

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.

Seizures associated with alcohol intake: to abstain or not to abstain that is the question

A reader of my blog wrote in to me. As has been the trend, I try to answer each and every question though lately I have to admit I have fallen back in this quest mostly due to constraint of time. I promise to be more timely in my replies going forward.

 

Here is his question. My answer to it follows:

 

HI, I was 21 when I had a seizure, following a weekend long music festival and drinking heavily and consuming amphetamines. Had about 5 or 6 following this up to the age of 25, mostly following drinking heavily and sometimes consuming amphetamines and/or diazepam. Have not taken any illegal substances since and now in my 30′s. Still drink regularly. No seizures and spent a few years taking a very low dose-100/200mg of epilim chrono(sodium valporate). Have not taken medication for 4 yrs approx. A junior doctor told me(while the consultant had left the room to fetch something) that he had studied this for his theses and it was very common for young adult males to “develop” seizures but assured me I would grow out of it, which appears so far(touch wood) to be true. Is there any truth in this? Is my case prob related to drink/illegal substance misuse?

 

S

 

 

Brain diseases reply:

 

Dear S,

Thank you for writing in to me at www.braindiseases.wordpress.com. I shall answer your question to me in a unique way. Here we go.

 

As a neurologist with interest in epilepsy I frequently encounter patients with history similar to yours. After a night of heavy drinking (usually different types of alcohol are consumed over a short course of time), at times along with other illicit drugs such as cocaine, amphetamines and more commonly prescription drugs such as Xanax and Valium (diazepam), lo and behold the person is witnessed to have a generalized convulsion soon there after (either that night itself or early next morning). The first encounter these patients have with the health care system is in the ER to which they present or are brought to by the EMS for evaluation. Now imagine that you are a physician in the ER and evaluate such a patient in the middle of the night. You are pressed for time. What shall be your assessment and plan? You shall order a few basic blood tests and a CT scan of the brain. CT scan comes back normal and the basic labs are normal too. Most of the times these patients are discharged from the ER after starting them on an anticonvulsant  (sodium valproate, phenytoin (Dilantin) and levetiracetam (Keppra) are the most commonly chosen drugs) with advice to follow up with a neurologist like me.

 

Now you may think that this “case” is closed but that is a fallacy.

 

Many questions remain unanswered:

 

  1. Was the seizure indeed induced by alcohol and the combination of illicit drugs? How sure are we of this fact? :  if this is indeed a seizure induced by alcohol and illicit drug use then surely the patient does not need an anticonvulsant drug. If he stops drinking/binging and stops illicit drug use he shall not have any more seizures.
  2. How long should the anticonvulsant medication continue?
  3. Can he drink a “little” amount or is alcohol completely off the bargaining table? Does he have to abstain for life?
  4. Who was the actual culprit—alcohol alone Vs alcohol in excess Vs alcohol and illicit drug combination Vs illicit drug by itself?
  5. Does the patient have an underlying seizure disorder (tendency to have seizure/ underlying epilepsy) and that alcohol/illicit drug combo was just the fuse. Such a patient of course shall warrant treatment with an anticonvulsant. Again more questions: which anticonvulsant and for how long? Does he need to be treated for life? If he takes an anticonvulsant can he again start drinking?

 

There is no one right answer to the above questions. No one size fits all model here. The answer to each has to be personalized to the patient at hand. Fortunately to answer the above questions as a neurologist I do not need expensive tests. All I need to do is to spend time with the patient and get a thorough history. In some cases I may order an electroencephalogram (EEG).

 

The rest is easy. Hope you found my answers insightful.

 

Nitin Sethi, MD

Side-effects associated with anticonvulsant use

Anticonvulsants (anti seizure medications) use is associated with various side-effects. Some of these can be troublesome. In this post I shall briefly list a few of the side-effects common to a number of anticonvulsants. As always my advise remains unchanged. The information provided here is no substitute to an actual visit to your physician. But I hope this post shall make you better informed.

Rash: can be associated with the use of a number of anticonvulsants. Phenytoin, lamotrigine, carabamazepine are the anticonvulsants commonly associated with rash. The rash may be mild or it may become quite fulminant leading to involvement of the mucous membranes (Steven Johnson Syndrome). The rash usually appears right at the onset (meaning a few days after the medication is started) but it may also appear at any point of time during the course of therapy. If rash is documented the usual advise is to stop the medication and consult your physician as soon as possible. Please remember though that sudden stoppage of anticonvulsant is not advisable since it may lead to a flurry of seizures. So it is your doctor who shall be the best person to make the decision: either stopping the medication cold turkey and substituting another anticonvulsant in its place  or slowing down the upward taper of the anticonvulsant and allowing the rash to subside.

Cognitive side-effects: a number of anticonvulsants can cause cognitive side-effects. Patients may complain of feeling dull (“I do not feel as sharp as usual” or “my mind is in a fog”). Some complain of difficulty concentrating and focusing while others have word finding difficulty (has been reported with the use of topiramate). Again if you experience any of these side-effects bring them to the attention of your doctor. At times lowering the dose of the anticonvulsant leads to resolution of these side-effects. At times taking the bulk of the anticonvulsant at night (larger dose at night and smaller dose in the morning) may be helpful since you can sleep off most of the side-effects.

Bone loss: many anticonvulsants lead to bone loss. The most commonly cited culprit drugs are phenytoin, carbamazepine and phenobarbital. Prolonged use of these anticonvulsants leads to bone loss and osteoporosis. That is the reason why your physician may advise you to supplement calcium and vitamin D. How much calcium and vitamin D to take on a daily basis though? The National Osteoporosis Foundation and National Institute of Health has given recommendations for daily calcium and vitamin D intake and most of the physicians refer to these.  Again your physician shall be the best person to determine how much calcium and vitamin D supplementation is required based on your age, the various medications you are taking and your risk of osteoporosis in the future. He may refer you for a bone densitometry test (commonly referred to as a DEXA scan).

Congenital malformations (major and minor): this applies to women of child bearing age who are exposed to/ taking anticonvulsants. Data from various pregnancy registries collected over many years has now informed us that anticonvulsant use by a woman during pregnancy may at times lead to major or minor malformations (cleft lip, cleft palate, congenital heart disease, spina bifida and so forth) in the baby. The risk though varies with some anticonvulsants “safer” than others.  No anticonvulsant though is completely free of this risk and again it is your doctor who shall be the best person to advise you about this.  The choice of an anticonvulsant in a woman of child bearing age is made after due consideration of the above risk. Folic acid supplementation before and during pregnancy may help to mitigate some of this risk to some extent.  So it is imperative that all women of child bearing age who are on anticonvulsants (and are contemplating pregnancy) should have a discussion about the risk of congenital malformations with their doctors.

Mood changes: anticonvulsants can lead to mood changes. Studies have shown that some are more likely to do so than others. Patients may complain of low mood, caregivers may notice that the patient is more agitated, snappy or restless. Some patients may become depressed. Hence the FDA has issued a warning on anticonvulsants and the risk of suicide and suicidal thoughts. Again your physician shall be the best person to decide which anticonvulsant is appropriate for you.

Apart from the above mentioned side-effects, each anticonvulsant has side-effects which are unique to it.  So it is important that you read the package insert and tell your doctor about any other medical conditions that you may have. Also mention other medications that you taking so that your doctor can determine and tell you about important drug-drug interactions.

I hope this information helps some of the readers of my blog.

 

Nitin Sethi, MD

Seizures: a question and an answer

One of the readers of my blog wrote to me recently. His question and my reply to it follows. I think some of you may find it helpful.

 

Hello Dr. Sethi,
 
I came to your site/blog while doing a Google search regarding delirium tremens, which I found extremely helpful!  So I thought I would ask for your opinion about a diagnosis my neurologist gave to me about half a year or so ago.  Please feel free to remove my email and name and post on your blog!
 
So my history is that I’m 20 years of age and have had two seizures in the past…36 months or so.  I have had no family history of seizures or epilepsy, one case each of diabetes (treated with metformin), stroke (no known treatment), and breast cancer (treated by partial mastectomy).  Both sides of my family are on high blood pressure medications.  I myself have a history of reactive airway disease.  I have also been prescribed lots of co-actifed and have developed a bit of an addiction to using drugs that cause sedation; among the things I can list are: codeine, diphenhydramine, Actifed, lorazepam, and tramadol (I would say this is probably significant), and I often self dose; with high amounts of codeine, and often double or triple the recommended doses for benadryl and Actifed (as on the box); these three are the most common drugs I take to sleep, I realize I am developing a tolerance to them.  I am trying to stop using these as a way of falling asleep. 
 
Anyway, so the first incidence of my seizure happened when I was working on my computer, writing up a laboratory report that I was working on for a while.  I had been sitting there for several hours already.  I had been taking tramadol on and off for the couple of months or so.  I fell into a seizure and my mother found me.  Nobody saw what happened as I slipped into a seizure, I just fell backwards. 
Key things I remembered/observed:
-I did not have an aura
-I did not have incontinence
-I instinctively bit down, but I do not know if I bit my tongue because my mom had put her finger in my mouth
-I had nausea when I woke up
-The whole sequence of events I believe lasted around 5 or so minutes. 
 
The ER doc and the paramedics had concluded the seizure was due to tramadol. 
 
The second incidence of seizure happened when I was sleep deprived, though arguably I was sleep deprived in the first incidence too.  I had only slept several hours the night before and I did not nap (which I usually do for several hours during the day).  I spent the whole day awake, and I went to a friend’s house afterwards.  I was playing a poker game, which often makes me feel really stressed (I get sweaty palms, feeling of coldness, a bit of light-headedness, and sometimes I get slight dizziness).  I remember that I had not eaten much at dinnertime and I was hungry, so I ate a bunch of chips as a snack, with an iced tea to drink.  I remember I had slipped into a seizure, again with the same symptoms as the first time, lasting about 5 minutes.  The key issue is that I did NOT bite my tongue. 
 
Again, I was taken to the ER and the ER doc was not sure what could have caused it.  I do not recall taking any drugs throughout the course of the day but I might have taken some diphenhydramine to sleep the night before.  I realize that these act on the nervous system.  The ER doc immediately prescribed me phenytoin and referred me to a neurologist, and an EEG ordered. My neurologist subsequently ordered an MRI.
 
 
When I went to see my neurologist, she examined me as usual and asked for the same details I have given above.  Her conclusion given her initial diagnosis was an epileptic seizure of cause unknown.  Her suspected trigger was sleep deprivation.  A second neurologist I visited repeated the diagnosis. 
 
Following the EEG and MRI, I went back to see my neurologist (this was after several visits).  The EEG had come back normal.  I did not lose consciousness (aside from the sleeping phase of the test) nor was ever informed that I had a seizure during the course of the test.  The MRI had also come back as negative in anything in my brain.  I was not informed of any other explanation other than a “possible” epilepsy condition.  Neurologist placed me on phenytoin, which I took for three weeks before having an allergic reaction and had to be switched over to levetiracetam.  Following that I saw the neurologist again due to severe depression and mood disorder.  We decided mutually not to take the medication, of which she warned me that there was a 75% chance of a third seizure in the following year. 
 
To this date, I have not had another seizure, and about 7 months has passed since the incident.  Again I have not taken any antiepileptics aside from occasional (several days to several weeks in between doses) lorazepam 1mg. 
 
I should note also that while having taken lorazepam 1mg-2mg (and being off of it for a week), I have subsequently drank more alcohol than I usually do and taken a ranitidine 150mg before going to drink (supposedly to prevent hangovers and being able to drink more).  The amount I drank was about 2 shots and a beer, before I started to experience delirium tremens.  The odd thing is, however, that exactly one week after that incident, I drank the same amount of alcohol but did not have delirium tremens (without having taken the ranitidine).  I understand how alcohol works in the brain by depressing the nervous system. 
 
I understand that the medication is preventative, but I am worried that I might have another seizure.  It puzzles me since my lack of taking medication should therefore result in seizures if I really have epilepsy.  I understand that drugs can cause seizures, especially in overdosing amounts, however, I would really like a second opinion about whether or not I really do have epilepsy.  Of course I understand that your opinion is only an opinion since I have not been examined by yourself, but I have provided as much relevant information as I can.  I also understand that there are many triggers of epilepsy, and often the cause isn’t really clear.  I would like to be seizure free of course and not have to take medication, but my neurologists are telling me otherwise, which concerns me. 
 
Please reply to me with your opinion as your time allows.  Oh please feel free to also use medical jargon if you wish in your replies, I am actually studying as a pre-med student myself, which might be where the stress is coming from. 
 
With Regards and thanks,
 
xx
Dear XX,
                               thank you for writing in to me. You gave me a very detailed and thorough history. While as a rule I do not and should not diagnose someone over the Internet since I have neither taken the history myself nor examined them, I do have a few words of advice. It is likely you have an underlying tendency to have a seizure. It is also well known that sleep deprivation, excessive use of over the counter antihistamincs and other prescribed medications such as lorazepam, codeine and Tramadol can lower the seizure threshold especially when you are mixing these medications with alcohol.
 
Let me explain in another way. Two of your doctors (ER physician and neurologist) feel that you have epilepsy and prescribed anti-convulsant therapy. A normal EEG and a normal MRI brain do not rule out epilepsy. Infact many epileptics may have a normal routine (40 minutes) EEG study. Hence to increase the yield sometimes a more prolonged EEG study is ordered (such as a 24 hour ambulatory EEG study or an inpatient video-EEG study). If the EEG study clearly shows interictal epileptiform discharges, it strengthens the argument that you suffer from epilepsy and that it shall be prudent to continue taking an anti-convulsant since the chance of a third seizure is high. On the other hand if the EEG study comes back normal, we are back to square one. It does NOT rule out epilepsy. Levetiracetam has been reported to cause psychogenic side-effects such as anxiety. It can also make patients frankly depressed. So a mutual decision between you and your physician was made to stop levetiracetam.
 
If I understand your email right, at present you are NOT on any anti-convulsant therapy. Your physician rightly informed you of the risks of taking this approach. You should remain in close follow up with your neurologist. Also since you have already suffered two convulsions (and have decided not to continue anti-convulsant therapy), it shall indeed be prudent if you make significant lifestyle changes. Namely avoiding alcohol completely or if that is not possible drinking in extreme moderation. I would also advice cutting down your use of over the counter sedatives, antihistaminics and other sleeping aids. You should maintain seizure and fall precautions at all times. Remember seizures are associated with falls and sometimes fatal injuries have occured. I always tell my patients  “you do not want to have a seizure at the wrong place and at the wrong time”. You should not drive as per the law of the state you reside in. Maintain good sleep hygiene and again remain in follow up with your physician. He/she shall be the best person to guide your care going forward.
 
Personal Regards,

Nitin Sethi, MD

Seizures associated with excessive alcohol intake-why me?

One of the readers of my blog asked a question about alcohol induced seizures. His question and my reply to it follows. I have removed the name to maintain confidentality as always.

QUESTION

Hi; I wanted to read up about alcohol induced seizures because I have a question(s) for you, but I guess I should give you a little background first. I have had 7 of them, never had a problem before. The first one I do remember…I was drinking heavily ( Vodka ) and had done some recreational drugs too. I was in the kitchen and my bottom jaw “stuck” out and my hands clinched tight! My brain said “lay down” so I did and that’s as much as I remember. My soon to be wife and my son told me that my lips turned blue, eyes rolled up and I “wet” myself.Needless to say they called 9-11 but I refused to go.The other 6 six I do not remember…although the last one happened in the street and I got 3 staples in the head as a result.My Dad was an alcoholic so I never really drank growing up.However,when my son’s mother and I split when he was 2 ( he is 16 now ) I started to drink more, I had socially here and there but not like this.The seizures started about 3+ years ago I would “guesstimate”.I tried rehab 3 times – no good.At my “peak” I was drinking a gallon of Vodka a day.( I am not making any of this up! ).I have had massive panic attacks,spent hours ( every 20 min.) over the toilet,my blood pressure was through the roof and on and on.The “nail in the coffin” for me was one day I had my “other half” leave work to bring me my fix because I couldn’t handle the with-drawls any longer that morning. I drank about a pint and had pain in my chest,irregular breathing and I honestly felt like I was going to die!!My neighbor took me to emergency.When my “other half” got wind of it and showed up I was in horrible shape. The Doctor told her my blood-alcohol was .335 and he wanted to know how come I was even still functioning.( I know nothing of the point scale but I assume that was pretty bad ).I spent 3 days there, 2 on a heart monitor.They gave me Valume ( I don’t think I spelled that right ) and I don’t know what else.I had been given Librium in the past but they did not give me any, nor did I have any seizures while I was there.I was however really scared.When I came home I swore to my family that that was it……..it will 2 years in April !!! I drink a lot of coffee ( w/milk and sugar of course )and I like my ice cream!I build and paint models to “occupy” myself around the house but I do still think about it ( drinking ) here and there.I’m really not to worried about starting again…all I have to do is think about what I put the people I love through and that pretty much ” kills ” any craving,but I am fully aware that I will always be an Alcoholic. I do have an excessive personality, I really can’t do anything in moderation and I have insomnia ( in other words I am VERY high strung to begin with ).I will say that life is sooooo much better now but I do have a couple of questions……Why all of a sudden?  20+ years of “partying” and then one night “boom”( or did I answer my own question? ).It did take awhile to get to a gallon a day ( a few years in fact ). On a bigger scale….what I really would like to know is am I done having them? I think about them once and awhile and it kind of scares me to think I could be out doing something and have another one.I abstain from alcohol and everything else, but I do miss being able to “socialize” like everyone else.I don’t mind when people drink around me, it doesn’t tempt me or anything ( plus I know what they are going to feel like later! ) but I guess I put myself in that “boat”. Am I done having them??? I haven’t had one since I stopped drinking although one night at work shortly after I stopped I did have some kind of “panic attack”( light head,scared,sweating,dizzy-I just went home ) been O.K since but that is what got me wondering if I am truly done w/them.( I cannot associate any pain or anything w/having them – just waking up disoriented in an ambulance or wherever else, but again….I am clean and sober and will stay that way so can I assume that there won’t be anymore?
And to anyone reading this….I am no expert on this and believe me, I don’t tell ANYONE how to live their life but –  if your to the point of having seizures from drinking like I did – time to quit the game and walk away! I was playing a game that almost cost me my life – wasn’t worth it!
Thank you for your time reading this and I look forward to your response.

ANSWER

Thank you for writing in to me. As the name of my post suggests the seizure/ convulsion in the above case is usually temporally associated with excessive alcohol use. I shall use your question to discuss alcohol induced seizures at length namely under the following points:

“I can drink but know exactly when to stop”: people frequently have this misconception (these are people who usually suffer from a drinking problem aka alcoholics but still feel they have their drinking under control). Now what is “excessive” for one may be the “norm” for another. So there is no hard and fixed limit about exactly how much alcohol can be “safely consumed” without provoking a seizure.  Some people can drink like a fish and still not suffer a convulsion and there are others who have suffered an alcohol induced convulsion after just a “few” drinks. In my experience some people are particulary good in knowing when to stop. They shall drink right up to the limit but then stop and “be okay”. That said I feel this is playing with fire and if you are drinking right up the edge, you are playing Russian roulette.  

Another misconception that I have encountered is that people frequently feel that if they drink top shelf vodka or scotch or more commonly wine they are immune from suffering the ill-effects of excessive alcohol intake aka a seizure. Again it is not the type of alcohol which is consumed that makes you prone to have a convulsion, it is the absolute amount consumed. So if you drink bottle after bottle of wine, you are just as likely to suffer a convulsion as when you consume excessive amounts of some bottle shelf vodka. Obviously it goes without saying that one can ‘safely” cosume more bottle of light beer than an alcoholic beverage with a higher quantity of absolute alcohol.

When a person has suffered a convulsion in the field is brought to the emergency room, doctors as a rule usually check the blood alcohol level. This gives a fair indication about exactly how much alcohol was consumed and helps us in determing if excessive alcohol ingestion played a role in the seizure. The absolute blood alcohol level though is just a number and other things have to be considered before a seizure is attributed to excessive alcohol inake:

how long ago was the last drink consumed?  (alcohol is rather quickly metabolized and hence one may obtain a falsely low reading if the blood level is checked after some time has lapsed since the last drink).

over what time frame was the alcohol consumed ?(you are more likely to suffer a convulsion if you consume excessive amounts over a very short interval of time–aka if you are binge drinking). The caveat to that is alcohol withdrawal seizure if which a person who is a chronic alcoholic abruptly ceases drinking and suffers a withdrawal seizure. This usually occurs 24-48 hours after the last drink was consumed.

whether the drinks were mixed? one is more likely to suffer a convulsion in the setting of consuming many different types of drink (vodka, rum, whisky, beer) in one sitting. Again my personal impression is that this is not because one consumed different kinds of drinks, it is because when drinks are mixed you are more likely to consume more alcohol and not get a warning about when to stop.

whether there was use of illicit drugs along with the alcohol? combining alcohol and illicit drugs like cocaine, heroin and even prescription drugs like Xanax (a common drug of abuse), valium, Adderall, anti-depressants such as Wellbutrin, and even some over the counter so called safe herbal medications to lose weight can build the perfect storm to provoke a convulsion.

whether there were other precipitating factors? factors like been sleep deprived, dehydrated, drinking on an empty stomach all help in adding their two cents to build the perfect storm leading to an alcohol induced convulsion.

is there an underlying tendency/predisposition to have a convulsion? this concept is a little difficult to explain but let me attempt to explain with an example. Let us assume you have underlying epilepsy. You are then more likely to suffer a convulsion in the setting of excessive alcohol use that say a person who does not have underlying predisposition to have a seizure. You may both consume the same drinks and the same amount of alcohol, still you remain at higher risk of suffering a convulsion than the other person.

I thank you for your question and wish you good health in the New Year 2011. It takes immense strength of character and determination to walk away a winner from an alcohol addiction.

Personal Regards,

Nitin Sethi, MD

Syncope Vs Seizure: the quest for an answer

One of the readers of my blog sent me an interesting query. Here is her history. My response to it follows. I have deleted her name and hidden her email address to maintain her confidentiality.


HISTORY

Hi! I was grocery shopping in Wal-mart when I had my episode. I was walking to the front of the store after shopping for about an hour. My vision kept blacking out. It was like someone just turned out the lights. I would be able to see again and I would be standing there staring at something. This happened about 4 or 5 times over a ten minute span. The next thing I knew I was waking up in the hospital. Apparently I hit the ground started convulsing, my eyes rolled back and I was foaming at the mouth. I bit the side of my tongue, my body was horribly sore the next couple of days, but I didn’t have any bladder issues. I had no memory of the seizure or what had happened. I kept going in and hour for the next couple of hours. I busted my head on the floor which required staples. I had memory problems and balance issues for the next week. I then made an appointment with a neurologist. He thinks I have syncope. He sent me for my EEG to rule out epilepsy, but we haven’t got the results back yet. While I was having my EEG I started having facial spasms during the flashing light portion of the test. I’m reading about syncope and some of it just doesn’t fit. I am a HUGE salt eater. I crave salty foods all day! So if that was it, wouldn’t my diet be treating the syncope? Also, my sister has epilepsy. Her seizures are triggered by flashing lights. I have never had a seizure before. I have passed out in the past, but it was because of hypoglycemia. I don’t have any issues with heat or pain or seeing blood. It just doesn’t affect me. I just don’t know if he’s got the correct diagnosis and would like someone else’s opinion. Thanks!

Dear A,
                 thank you for writing in to me.  Your history has intrigued me and hence I shall dwell over it a little before offering my humble opinion.  It goes without saying, this opinion is offered without taking your history in person and examining you.  You should follow what your doctor tells you.  He/ she shall be the best person to guide further diagnostic and management issues.  Your recent event had features of both syncope as well as a seizure/ convulsion. So what in your history points towards syncope?
PRODROMAL FEATURES: meaning things which you felt prior to passing out. You felt light headed, your vision was blurred/ tunneled/ kept going in and out (it always fascinates me how patients use different words to describe the same symptom). Prior to a syncopal event patients may feel as if they are about to pass out/ faint. They may look pale (all the blood was drained out from the face), they may feel/ complain that their legs feel weak/ woobly.
I am uncertain what to make of the staring episodes which followed soon after. By staring do you mean you were unable to concentrate (may occur with syncope) or do you mean you had impairment in your level of consciousness and awareness ( goes more towards a seizure).
Anyways let us move forward. The next thing you remember is waking up in the hospital. From the bystander history, you were noticed to have convulsive movements. During the seizure, you lost body tone leading to a hard fall which cracked open your skull.  During the convulsion itself your eyes rolled back into your head, you foamed from the side of the mouth and bit the side of your tongue. Yes biting the side of the tongue goes more towards a seizure than biting the tip of your tongue. I am not sure who figured that one out though. You did not have loss of bladder control. Post the seizure, you were not yourself  for the next few days with a slow return to the baseline.
There I think I have summarized your history well. Well what happens next? Your history has features of both syncope as well a seizure.  I would have asked a few more questions:
1) did you feel anything prior to the event. We call these auras. Any strange smell, any strange taste and so forth.
2) have you ever had a seizure before.
3) any history of febrile convulsions?
4) are you prone to syncope: were you dehydrated, sick with the flu and so forth.
Well let us move forward. I am taking you step by step as I work through this history. So the doctor ordered an EEG (test to look at the brain waves). Why the EEG? Well simple if the EEG shows abnormal brain waves (I use the word misfiring of the brain), it points towards a seizure. If the EEG is normal, it may point towards syncope. That said and done, patients with seizures may have a normal EEG.
We do not have the EEG results. But during the test you mention something happened to you. Your face started twitching while photic stimulation was been carried out (flashing lights). Your sister has epilepsy and you say her seizures are triggered by flashing lights (usually patients who have primary generalized epilepsy have these kind of seizures).
So where does all this lead to?  My opinion: it is possible you have an underlying seizure disorder.
My recommendations: I would try my level best to rule out or rule in seizures. This may need a longer duration EEG study, if the first one is unrevealing. The decision to start anti-convulsant therapy shall be guided by all the above : history, examination findings, EEG findings and neuroimaging findings (CT scan or MRI brain).
THE BEST PERSON TO MAKE THAT DECISION–YOUR CURRENT DOCTOR AND NOT ME OVER THE INTERNET.