Milena Pavlova, MD

The case of a patient with breathing abnormalities caused by epilepsy.

By Milena Pavlova, MD

Epilepsy affects nearly 1% of the population. Approximately one third of the patients continue to have seizures despite therapy. Seizures may provoke multiple autonomic disturbances, including tachycardia, cardiac arrhythmias, and breathing disturbance. They also may often be seen during sleep and disrupt it. Mr SZ, a patient with lifelong epilepsy, experienced subtle hypopneas prior to a seizure and marked obstructive hypopneas and apneas after a seizure. Interventions, including CPAP, helped control breathing abnormalities, decrease seizure frequency, and prevent potentially life-threatening complications.

BACKGROUND

Breathing abnormalities have been described in patients with epilepsy in several case reports. For example, Singh et al1 and Hewertson et al2 report central apneas during seizures.

The two largest human studies have included 30 to 37 patients. In adults, Nashef et al3 described a number of respiratory disturbances, which varied with the intensity of the seizure. In their series, there were three secondary generalized seizures and all three were associated with an apnea. Additionally, of 35 complex partial seizures, they observed that 16 had an associated apnea. In two of these three seizures, there were also obstructive apneas seen post-ictally.

The largest study in children was reported by O’Regan et al.4 These authors described that, in a series of 40 focal seizures, there were ictal apneas seen in 12; postictal apnea in one; and hypoxemia below 85% in 15 of the 40 seizures. Tachypnea was observed in more than 50% of focal seizures. The degree of breathing disturbance likely depends on the location and severity of the seizure, and possibly the characteristics of the individual patient.

Table 1. Polysomnography findings.

HISTORY

Mr SZ was a 30-year-old man with lifelong epilepsy due to cortical dysplasia in the right occipital region. He had been treated in our clinic for many years. He was experiencing several types of seizures: dizzy spells, myoclonic seizures, partial seizures with focal tonic activity, and secondary generalized seizures. Typically, the seizures would occur in clusters—or three to five seizures occurring within the same day and predominantly in sleep. Frequency was severe; he often had daily events, despite combinations of two or more antiepileptic medications. After he continued to have intractable seizures despite multiple medications, he was treated with a vagal nerve stimulator.

Due to reports of snoring, and to further evaluate for potential causes of poor seizure control, the patient was referred for polysomnogram evaluation. At the time of presentation to the laboratory, he was treated with a vagal nerve stimulator, and a combination of lamotrigine and divalproex, as well as added lorazepam at the time of a seizure to prevent clustering.

POLYSOMNOGRAPHIC FINDINGS

The patient underwent an attended in-laboratory polysomnogram with “split night” protocol. Recording montage included EEG, EOG, EMG, ECG, nasal thermistor flow, nasal pressure, pharyngeal snoring, respiratory effort (two channels), anterior tibialis EMG, SaO2, and body position. Positive airway pressure (PAP) was initiated after the patient demonstrated clinically significant obstructive sleep apnea. This study was performed in accordance with the AASM scoring manual.

SLEEP STRUCTURE

The patient fell asleep in lateral position 18 minutes after the start of the recording. There was only NREM sleep seen.

Figure 1. Breathing before the seizure.

EPILEPTIC EVENT

About 30 minutes after sleep onset, the patient had an event, characterized as follows: At 0:10, from stage 2 sleep, while on the left side, the patient had bilateral upper extremity extension, followed by head hyperextension. Subsequently, there was a brief vocalization. Eyes were not clearly visible during the event. The seizure ended with an awakening. There were no clonic movements, no tongue biting, and no incontinence. The total duration of this event was 1 minute.

After the seizure, the patient was described as briefly confused. He was asked to recall three words stated by the technologist immediately after the event, but could not. Eight minutes after the seizure, the patient was able to recognize his father but not the technologist. He fell asleep within 12 minutes after the end of the seizure, this time in supine position. Thus, the patient had a complex partial seizure followed by a brief postictal state.

BREATHING BEFORE SEIZURE

Average respiratory rate was 15 breaths per minute in the minute immediately preceding the seizure onset (range from 12 to 15 in the 5 minutes prior to that).

Average oxygen saturation was around 96%. Heart rate ranged from 66 to 72 beats per minute. The patient was in lateral position. A typical 2-minute page of the polysomnogram during this period is displayed in Figure 1.

BREATHING DURING THE SEIZURE

Immediately after the seizure onset, there was a suppressed breathing effort with several seemingly erratic breaths in the first 22 seconds (not meeting classic criteria for central apnea), followed by tachypnea—with a respiratory rate of 29 breaths per minute in the 2 minutes that follow, which subsequently diminishes to 20 breaths per minute (shown on a 60 second page in Figure 2). Heart rate ranged from 130 to 144 beats per minute.

Figure 2. Breathing during the seizure.

BREATHING AFTER SEIZURE (BEFORE CPAP)

Average respiratory rate ranged from 15 to 19 breaths per minute in the 5 minutes of sleep after the seizure ended (approximately 5 minutes after the end of the seizure). Average oxygen saturation was around 95% in the absence of hypopneas. Minimum oxygen saturation was 79%. There was frequent and loud snoring during this portion of the study. Average heart rate was 74 to 81 beats per minute. The patient was in supine position. A typical 2-minute page is displayed in Figure 3.

AFTER CPAP

PAP was titrated from 5 to 7 cm of water pressure. At 7 cm, breathing was regular, and there were less than five respiratory abnormalities per hour, even in supine position. Oxygen saturation remained above 90%. The treatment was reasonably well tolerated.

FOLLOW-UP

Although the patient tolerated PAP relatively well in the laboratory, he had some difficulty tolerating it at home, and as a result compliance was not consistent. An oral appliance was considered to have a high aspiration risk, due to his frequent seizures, and surgery was declined. However, after addition of topiramate, and subsequently losing 18 pounds, he had some improvement in alertness and seizure control. He eventually had intervals of nearly 2 weeks being continuously seizure free (a substantial improvement considering prior frequency).

DISCUSSION

In this patient, we observed rare, subtle hypopneas prior to the seizure and, while the patient was in supine position, irregular breathing with some suppression of respiratory effort during the seizure, and frequent and marked obstructive hypopneas and apneas after the seizure, and while the patient was mostly in supine position. These abnormalities were controlled on CPAP at a relatively low pressure, in supine position.

Figure 3. Breathing after the seizure and before CPAP.

The more severe respiratory obstructive events seen post-ictally could be due to several causes:

  1. Positional worsening as seen in many patients with obstructive sleep apnea;
  2. Effect of the seizure (either hypotonia or impaired respiratory control post-ictally);
  3. Combination of factors.

Regardless of the cause, there was improvement in breathing seen within the same night, after CPAP was applied.

It is important to recognize and treat respiratory abnormalities in patients with seizures, as the respiratory abnormalities themselves can further lead to more severe autonomic abnormalities. For example, Nashef et al3 described in one patient a pattern of irregular and infrequent breathing, which ended with a central apnea and subsequently with a cardiac arrest. Furthermore, unwitnessed breathing abnormalities may be associated with the higher frequency of sudden unexpected death among patients with epilepsy.5 On the other hand, OSA, if present, may worsen seizure control6 and treatment of even mild OSA may lead to some improvement.7 Thus, regardless of the primary cause of breathing disturbance, treatment is needed to prevent worsening of epilepsy and potentially life-threatening complications.


Milena Pavlova, MD, is an instructor in neurology at the Brigham and Women’s Hospital/Harvard Medical School, Boston. She is also the medical director at the Faulkner Hospital Sleep Center. She is involved in multiple research projects on the interaction between sleep and medical and neurological disorders, including sleep, circadian rhythms, and epilepsy. Recent publications include “Is There a Circadian Variation of Epileptiform Abnormalities in Idiopathic Generalized Epilepsy?” (Epilepsy and Behavior. 2009;16:461-7). She can be reached at sleepreviewmag@allied360.com.

REFERENCES

  1. Singh B, Al Shahwan S, Al Deeb S. Partial seizures presenting as life-threatening apnea. Epilepsia. 1993;34:901-903.
  2. Hewertson J, Boyd SG, Samuels MP, Neville BGR, Southall DP. Hypoxemia and cardiorespiratory changes during epileptic seizures in young children. Dev Med Child Neurol. 1996;38:511-522.
  3. Nashef L, Walker F, Allen P, Sander JW, Shorvon SD, Fish DR. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry. 1996;60:297-300
  4. O’Regan ME, Brown JK. Abnormalities in cardiac and respiratory function observed during seizures in childhood. Dev Med Child Neurol. 2005;47:4-9.
  5. Langan Y, Nashef L, Sander JW. Case-control study of SUDEP. Neurology. 2005;64:1131-3
  6. Chihorek AM, Abou-Khalil B, Malow BA. Obstructive sleep apnea is associated with seizure occurrence in older adults with epilepsy. Neurology. 2007;69:1823-7.
  7. Malow BA, Foldvary-Schaefer N, Vaughn BV, et al. Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot trial. Neurology. 2008;71:572-7.