Transient Amnesia Secondary to Metastatic Carcinoma Misdiagnosed as Anxiety Problem
Mrs. W, a 72-year-old female, was admitted to a senior behavioral health inpatient unit following two episodes of transient amnesia. The first episode occurred following a near motor vehicle accident in a parking lot while she had been driving alone in her car. Immediately afterwards, she moved to the passenger’s seat where she was found by security guards, to whom she reported that she could not remember how to operate her car. Mrs. W was disoriented to situation and place but was able to provide her daughter’s name and phone number. She was taken to a community hospital emergency department (ED) and underwent an evaluation. Laboratory tests including a complete blood count, cardiac markers, a basic metabolic panel, and liver function tests were normal with the exception of an elevated total serum protein of 8.9 g/dL. Her electrocardiogram was normal. Chest radiograph and head computed tomography (CT) scan were performed.
The patient was diagnosed with “acute anxiety” and discharged with a prescription for alprazolam. The radiological studies were not reviewed by the ED doctor or discussed with the patient or her family prior to discharge. Mrs. W and her family were not contacted regarding these studies after discharge.
One week later, the patient had a second amnesic episode while driving. She recalled leaving her house, and the next thing she remembered was driving in Mexico and being lost. After several hours, Mrs. W found her way back across the border and telephoned her daughter, who picked her up and brought her directly to the senior behavioral health inpatient unit, where she was admitted.
Transient global amnesia (TGA) is a syndrome characterized by acute onset of anterograde amnesia accompanied by variable retrograde amnesia. Episodes last less than 24 hours and most often occur in older adults. During the amnesic period, patients recall their identities and recognize familiar people, but they cannot remember recent events and are unable to acquire new information. The memory loss is accompanied by disorientation and repetitive questions. Patients appear bewildered and confused but have insight into their memory problem. Patients are usually free from neurological deficits, but difficulty copying complex constructions has been observed in the midst of an episode.1
The cause of TGA continues to be a matter of debate. A vascular mechanism is most commonly described.2 Vascular causes of TGA include basilar artery thrombosis, transient ischemic attack (TIA), posterior circulation arterial stroke, migraine, and venous congestion. The venous congestion hypothesis is supported by the association between TGA and circumstances that result in reduced venous return and retrograde venous blood flow, such as the Valsalva maneuver, stress, pain, sexual activity, or excessive exertion. On positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWMRI) scans, transient disruption of blood flow to specific brain areas including the thalamus and mesial temporal structures may be seen.3,4
Although TGA is considered a benign disorder and is rarely associated with intracranial lesions, other causes of transient amnesia include brain tumors, seizures, and psychiatric disorders including dissociative disorders.1 Transient amnesia associated with tumors is believed to occur when there is bilateral involvement of the temporal lobes or unilateral involvement with associated bilateral ischemia.5-7 In addition to transient ischemia, other suggested explanations of the etiology of transient amnesia in patients with brain tumors include hemorrhage within the tumor and complex partial seizures. Although TGA has been described in association with tumors, to our knowledge there is only one published case associated with metastatic lesions.5
TGA has occasionally been associated with temporal lobe spikes on electroencephalogram (EEG),8 epilepsy,9 and subclinical rhythmic EEG discharge.10 Amnestic episodes in patients with partial complex seizures may last several hours. Amnestic episodes secondary to partial complex seizures and post-ictal states differ from TGA in that the amnesia is preceded by stereotyped symptoms and is associated with sleepiness, confusion, disorientation, and behavioral withdrawal (Table I).11,12 Some authors recommend that the term transient global amnesia be reserved for idiopathic short-lived amnesia or for cases when the mechanism of the amnesia cannot be identified. If the amnesia is believed to be caused by a seizure disorder, then the term transient amnesia secondary to seizure is recommended.13
The differential diagnosis of TGA also includes dissociative states, which are the result of disturbances in the normally integrated functions of identity, memory, and consciousness.14 Dissociative states are sometimes the result of neurological disorders such as partial complex seizures, intoxication with sedative-hypnotic medication or alcohol (blackouts), or may have a psychological origin such as dissociative identity disorder (formerly multiple personality disorder), dissociative fugue (formerly psychogenic fugue), and dissociative amnesia (formerly psychogenic amnesia). A psychogenic fugue occurs when a person suddenly travels away from usual places, assumes a new identity, and has amnesia for his or her past. In cases of dissociative amnesia, the individual does not assume a completely new identity but has circumscribed amnesia for an event that is psychologically helpful to forget due to its catastrophic, shameful, immoral, or illegal nature.
Outcome of the Case Patient
On admission, Mrs. W denied any complaints including symptoms of depression or anxiety, and reported that she had not used any alprazolam. (No confirmatory toxicology testing was obtained.) The patient’s daughter was concerned with Mrs. W’s vague speech and thought and with her interpersonally disconnected demeanor. She reported that the patient had been experiencing mild anxiety, depressed mood, and increased sleep for 3 months prior to admission. Two months prior to admission she began taking sertraline 50 mg daily for depression, and several days prior to her admission her dose was increased to 100 mg daily. According to the daughter, the patient was under considerable stress due to being the primary caretaker of her husband (who had Alzheimer’s dementia), her daughter’s recently diagnosed ovarian cancer, and her grandson’s ongoing symptoms of attention-deficit/hyperactivity disorder. Neither the patient nor her daughter reported any other past psychiatric history, including amnestic episodes, prior to those already described. Mrs. W’s medical history was remarkable for hypothyroidism and hypertension, and her family history was significant for her mother having agoraphobia. At the time of admission, she was alert and oriented in all spheres. Her physical and neurological examinations were unremarkable. She scored 25 out of 30 on the Mini-Mental State Examination (MMSE).15 (The patient missed one point for orientation, two points for inaccurate serial seven subtractions, one point for recalling only two out of three items after a brief delay, and one point for inaccurately copying the interlocking pentagons.)
The patient’s treatment team members were aware of previous research that demonstrated that new or worsened medical problems in older patients with behavioral symptoms are not infrequently overlooked.16 This awareness and the patient’s history of abrupt and dramatic new behavioral symptoms, combined with an elevated erythrocyte sedimentation rate (ESR), prompted a careful medical evaluation that included neuroimaging. Table II lists medical disorders and substances that are known to be possible causes of anxiety symptoms.
Initial laboratory studies were notable for normocytic anemia with hemoglobin of 10.9 g/dL and an ESR of 100 mm/h. Brain MRI scan demonstrated two nodular, rim-enhancing lesions in the gray-white junction with marked surrounding edema, one in the anterior high left frontal lobe and the other in the right parietal lobe, and both approximately 1 cm in diameter. Mrs. W’s chest CT scan demonstrated a spiculated, centrally necrotic right middle lobe mass, with extensive necrotic lymphadenopathy. An abdominal CT scan demonstrated a left adrenal mass. Tissue obtained through bronchoscopy revealed scattered atypia consistent with small-cell lung cancer.
The patient had a Neurology consultation, and her thought and memory disturbances as well as her amnesia were believed to be most likely the result of partial complex seizures.1 Due to the patient’s request for prompt treatment of her cancer, and to the realization that an EEG that did not show seizure activity would not rule out this diagnosis, no EEG was obtained. Although the Neurology consultation team believed that the patient’s amnesia was secondary to partial complex seizures, her primary team remained undecided about the precise etiology due to the absence of confirmatory historical information, such as witnessed automatisms or a post-ictal state that would have been present if the etiology of her amnesia was from seizure activity. In addition, although this patient’s imaged brain lesions were not anatomically located near memory structures, it is possible that she had metastases in the hippocampalfornical system that were too small to be seen on CT or MRI scan and, if present, they would also provide a possible explanation for her amnesia. Also, due to Mrs. W’s request for prompt treatment of her cancer, no cognitive testing other than her initial MMSE was accomplished. Treatment with phenytoin, however, was initiated, and the patient was then transferred to the Oncology service.
Mrs. W’s case was presented to the hospital Tumor Board, which concluded that the exact type of her cancer remained unclear, and a recommendation for a second tissue biopsy was made. It is not known whether she had any further amnestic episodes, and no additional attempts were made to obtain and evaluate the cancerous tissue. The patient underwent whole-brain radiation and began chemotherapy with cisplatin and etoposide. She was re-admitted to the hospital for pneumonia 6 weeks after her initial presentation and was subsequently discharged to her home with hospice care.
As this case demonstrates, TGA may result from medical problems and is not always benign. This may be only the second published report of a patient with transient amnesia from brain metastases, and in this case, probable metastatic small-cell carcinoma of the lung. This case underscores that amnesic episodes may be diagnosed incorrectly as a psychiatric problem such as an anxiety disorder. A number of aspects of the patient’s history may have contributed to a premature conclusion that the patient’s complaints were of psychiatric origin. Historical information that may have contributed to the initial incorrect diagnosis included her history of problems with depression and anxiety, her recent treatment with sertraline, her multiple significant life stressors, and her mother’s history of agoraphobia.
Imaging done at the community hospital following the first episode revealed a right middle lobe mass on chest x-ray, and left frontal and right parietal vasogenic edema with underlying lesions on head CT scan. Unfortunately, the patient was discharged from the community hospital ED prior to review of these images, leading to a delay of diagnosis and treatment of about 2 weeks. Diagnosing and discharging the patient from the community hospital ED prior to review of the tests that had been ordered is a basic error that should have been avoided. The resulting delay in accurate diagnosis and treatment may not have had a significant direct impact on her prognosis but certainly did expose the patient and others to a number of avoidable risks. For example, the cancer loci in her brain could have led to additional unsafe driving and a motor vehicle accident.
New or suddenly worsened behavioral symptoms in an older patient should be considered a sign of a possible undiagnosed underlying medical problem even in the presence of a history of recent psychiatric illness, a family history of psychiatric illness, or multiple confirmed sources of stress. In addition, this case serves as a dramatic reminder of the basic medical principle that when conducting a medical evaluation of a patient, every test result should be reviewed before making a final diagnosis and prescribing treatment.
This work was supported, in part, by grants from the National Institute of Mental Health, Department of Veterans Affairs, and the John A. Hartford Foundation.
The authors report no relevant financial relationships.
Author Affiliations: Drs. Hadley and Sewell are from the Division of Geriatric Psychiatry, Department of Psychiatry, and Dr. Daly is from the Division of Geriatric Internal Medicine, Department of Internal Medicine, University of California, San Diego.