EPI Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks This is not an actual case study. It has been adapted and developed from scientific literature as referenced. © Eisai Inc All Rights Reserved.

EPI During a regular annual visit to the pediatrician, parents of a 2-year-old girl report that she has disturbed sleep patterns. Specifically, they mention that approximately 90 minutes after falling asleep, she sits up in bed and screams. She appears to be awake, but seems confused. She is not aware of her parents’ presence and does not show any recognition or respond to their consolation. Occasionally, she walks around in bed. After about minutes, she falls back to sleep. The pediatrician suspects that these may be just benign nightmares. At the next visit, the parents report that the episodes of disturbed sleep are still occurring about once/month. They do not bring up any other symptoms. The pediatrician notes that the child is developing normally otherwise. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question

EPI During a regular annual visit to the pediatrician, parents of a 2-year-old girl report that she has disturbed sleep patterns. Specifically, they mention that approximately 90 minutes after falling asleep, she sits up in bed and screams. She appears to be awake, but seems confused. She is not aware of her parents’ presence and does not show any recognition or respond to their consolation. Occasionally, she walks around in bed. After about minutes, she falls back to sleep. The pediatrician suspects that these may be just benign nightmares. At the next visit, the parents report that the episodes of disturbed sleep are still occurring about once/month. They do not bring up any other symptoms. The pediatrician notes that the child is developing normally otherwise. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question: At this point, what do you think her diagnosis might be? Answer Data

EPI During a regular annual visit to the pediatrician, parents of a 2-year-old girl report that she has disturbed sleep patterns. Specifically, they mention that approximately 90 minutes after falling asleep, she sits up in bed and screams. She appears to be awake, but seems confused. She is not aware of her parents’ presence and does not show any recognition or respond to their consolation. Occasionally, she walks around in bed. After about minutes, she falls back to sleep. The pediatrician suspects that these may be just benign nightmares. At the next visit, the parents report that the episodes of disturbed sleep are still occurring about once/month. They do not bring up any other symptoms. The pediatrician notes that the child is developing normally otherwise. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Answer: At 3 years of age, the pediatrician diagnoses the child with night terrors. 1 Since the child seems to be otherwise normal and healthy, the parents are counseled that these episodes tend to disappear with age. Next Data Question

EPI Indeed, the episodes of night terror disappear by the time the child is 5 years old. There are no further significant issues in her development until the age of 12. Between the ages of 12 and 14 years, sudden temper tantrums develop. Initially these are rare, but they worsen over time. At 14 years of age, the girl is referred to a pediatric psychiatric center because of behavioral problems at school. School reports indicate that she has outbursts of temper followed by short bouts of depression. She is counseled by an educational psychologist and her condition improves. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question

EPI Indeed, the episodes of night terror disappear by the time the child is 5 years old. There are no further significant issues in her development until the age of 12. Between the ages of 12 and 14 years, sudden temper tantrums develop. Initially these are rare, but they worsen over time. At 14 years of age, the girl is referred to a pediatric psychiatric center because of behavioral problems at school. School reports indicate that she has outbursts of temper followed by short bouts of depression. She is counseled by an educational psychologist and her condition improves. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Answer Data Question: What other issues would you consider in further evaluating this case?

EPI Indeed, the episodes of night terror disappear by the time the child is 5 years old. There are no further significant issues in her development until the age of 12. Between the ages of 12 and 14 years, sudden temper tantrums develop. Initially these are rare, but they worsen over time. At 14 years of age, the girl is referred to a pediatric psychiatric center because of behavioral problems at school. School reports indicate that she has outbursts of temper followed by short bouts of depression. She is counseled by an educational psychologist and her condition improves. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question Next Data Answer: This girl’s symptoms appear to be psychiatric in nature. 1 However, other differential diagnoses need to be kept in mind. The parents need to be counseled on the appropriate follow-up.

EPI Approximately 1 year later, the patient is referred again with similar problems. She now complains of recurrent episodes of acute anxiety, accompanied by palpitations, hyperventilation, fuzziness in the head, strange sensations in the stomach, tightness in the chest and throat, nausea, and an urgency to urinate. Her parents report that during these episodes, she screams and runs around in an agitated state. The attacks are brief, lasting about 1-2 minutes, and occur mostly during the day. However, they occasionally occur at night. Immediately prior to the nightly attacks, she wakes up, and her parents describe her as appearing dazed and distant. The patient states that she is aware of her actions but unable to control herself. She is perplexed by her exaggerated outbursts at seemingly trivial events. She is taking a contraceptive pill, but denies use of recreational drugs. The physical- and mental-state examinations are normal. There is a family history of generalized anxiety (father) and epilepsy (paternal grandmother and paternal aunt). Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question

EPI Approximately 1 year later, the patient is referred again with similar problems. She now complains of recurrent episodes of acute anxiety, accompanied by palpitations, hyperventilation, fuzziness in the head, strange sensations in the stomach, tightness in the chest and throat, nausea, and an urgency to urinate. Her parents report that during these episodes, she screams and runs around in an agitated state. The attacks are brief, lasting about 1-2 minutes, and occur mostly during the day. However, they occasionally occur at night. Immediately prior to the nightly attacks, she wakes up, and her parents describe her as appearing dazed and distant. The patient states that she is aware of her actions but unable to control herself. She is perplexed by her exaggerated outbursts at seemingly trivial events. She is taking a contraceptive pill, but denies use of recreational drugs. The physical- and mental-state examinations are normal. There is a family history of generalized anxiety (father) and epilepsy (paternal grandmother and paternal aunt). Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Data Answer Question: What diagnosis would you consider at this point? Please clarify what additional considerations or concerns you would take into account to confirm your diagnosis.

EPI Approximately 1 year later, the patient is referred again with similar problems. She now complains of recurrent episodes of acute anxiety, accompanied by palpitations, hyperventilation, fuzziness in the head, strange sensations in the stomach, tightness in the chest and throat, nausea, and an urgency to urinate. Her parents report that during these episodes, she screams and runs around in an agitated state. The attacks are brief, lasting about 1-2 minutes, and occur mostly during the day. However, they occasionally occur at night. Immediately prior to the nightly attacks, she wakes up, and her parents describe her as appearing dazed and distant. The patient states that she is aware of her actions but unable to control herself. She is perplexed by her exaggerated outbursts at seemingly trivial events. She is taking a contraceptive pill, but denies use of recreational drugs. The physical- and mental-state examinations are normal. There is a family history of generalized anxiety (father) and epilepsy (paternal grandmother and paternal aunt). Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question Next Data Answer: Symptoms continue to appear psychiatric in nature, with many features suggestive of panic attacks. However, some of the features are atypical: their durations are particularly short, and there is prominent motor activity and nocturnal occurrences. Given the family history of epilepsy, further investigation with electroencephalography (EEG) is recommended. 1

EPI Immediately before the EEG, the patient has an attack during which she appears anguished, flushed, cries out in panic, and leaps off the bed. She then becomes drowsy, but remains cooperative. The EEG shows bilateral frontal high-voltage continuous delta activity, concomitant with behavior characterized by confusion, hypotonia, and alternating gestural automatisms. EEG monitoring over the next 48 hours shows 2 similar episodes, each lasting about 40 seconds and corresponding with behavioral manifestations, as well as an additional 25-second burst of delta activity that remains asymptomatic. All blood tests and a computed tomography of her head are normal. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks EEG

EPI Immediately before the EEG, the patient has an attack during which she appears anguished, flushed, cries out in panic, and leaps off the bed. She then becomes drowsy, but remains cooperative. The EEG shows bilateral frontal high-voltage continuous delta activity, concomitant with behavior characterized by confusion, hypotonia, and alternating gestural automatisms. EEG monitoring over the next 48 hours shows 2 similar episodes, each lasting about 40 seconds and corresponding with behavioral manifestations, as well as an additional 25-second burst of delta activity that remains asymptomatic. All blood tests and a computed tomography of her head are normal. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Figure 1. EEG recording showed bilateral frontal high-voltage continuous delta activity, concomitant with behavior characterized by confusion, hypotonia, and alternating gestural automatisms. Data Question

EPI Immediately before the EEG, the patient has an attack during which she appears anguished, flushed, cries out in panic, and leaps off the bed. She then becomes drowsy, but remains cooperative. The EEG shows bilateral frontal high-voltage continuous delta activity, concomitant with behavior characterized by confusion, hypotonia, and alternating gestural automatisms. EEG monitoring over the next 48 hours shows 2 similar episodes, each lasting about 40 seconds and corresponding with behavioral manifestations, as well as an additional 25-second burst of delta activity that remains asymptomatic. All blood tests and a computed tomography of her head are normal. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks EEG Answer Data Question: What is your diagnosis now?

EPI Immediately before the EEG, the patient has an attack during which she appears anguished, flushed, cries out in panic, and leaps off the bed. She then becomes drowsy, but remains cooperative. The EEG shows bilateral frontal high-voltage continuous delta activity, concomitant with behavior characterized by confusion, hypotonia, and alternating gestural automatisms. EEG monitoring over the next 48 hours shows 2 similar episodes, each lasting about 40 seconds and corresponding with behavioral manifestations, as well as an additional 25-second burst of delta activity that remains asymptomatic. All blood tests and a computed tomography of her head are normal. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks Question Next Data EEG Answer: The final diagnosis is “Complex Partial Seizures” 1 or, according to the most recent revised classification and definitions of the International League Against Epilepsy, “Focal Seizures With Brief Loss of Consciousness”. 2 The patient is started on an appropriate anticonvulsant and her behavioral outbursts subside. Important Point: Partial seizures can manifest occasionally as a psychiatric disorder. A family history of seizure disorder is a valuable diagnostic tool. 1

EPI Note: Case description is adapted from the published case report presented in reference 1. Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks

EPI References Laidlaw JDD, Zaw KM. Epilepsy mistaken for panic attack in an adolescent girl. BMJ 1993;306: Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, Epilepsia 2010;51: Case Study 2: Complex Diagnostic Challenge of a Patient Presenting With Anxiety Attacks