Solving the Case of the Perplexing Symptoms

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CLINICAL

Like hotshot detectives from Scotland Yard, psychiatrists are often asked to make sense of mysterious situations. In the case described here, a young man was admitted to the hospital with perplexing psychiatric and neurologic symptoms. (The identifying details of the patient have been changed to protect the patient’s identity.) Since symptoms of medical disorders can mimic neuropsychiatric disorders, it would take careful interviewing and some detective work to arrive at the right diagnosis.

The Case Unfolds: The Initial Interview

“Roger,” a Hispanic male, aged 34 years, residing alone, presented to the emergency department with severe depression, marked by difficulty getting up in the morning for work, crying spells, chronic insomnia, and passive suicidal ideation—all worsening over the past 6 weeks. He complained of auditory and visual hallucinations, reporting that he “often heard voices muttering in the background,” although he could not decipher what they were saying. He also “sometimes saw shadows in the corner of the room.” He further noted that he was concerned about “missing a lot of work and forgetting things.”

According to Roger, he had been well until approximately 3 years ago when he began experiencing depression. He already had 2 prior psychiatric admissions at another hospital, about 2 months apart, with each hospitalization lasting 2 weeks. After the second discharge, about 6 weeks prior, he was referred back to his therapist in their outpatient clinic.

Roger was prescribed fluoxetine 20 mg by mouth (po) every morning (qAM), risperidone 1 mg po twice daily (BID), and benztropine 0.5 mg po BID. He admitted he was not as careful as he should be with medication adherence, noting that he takes the medications “some of the time. Sometimes I forget.” He complained that the fluoxetine had sexual adverse effects, reducing frequency of erections, and it “also interrupted my sleep.” He complained of ongoing fatigue and memory lapses.

He reported that he did not like the outpatient clinician, saying, “I never really felt comfortable with her.” He admitted missing a number of follow-up appointments at the mental health clinic. When the symptoms persisted, the patient “decided to try another hospital” and was admitted to our psychiatry unit.

The patient presented with severe depression with insomnia, decreased appetite, anhedonia, and increasing social withdrawal. Roger denied any suicidal plans, but he admitted to having passive thoughts of “not living anymore.” He firmly denied any history of suicide attempts and had no intention of harming himself. Roger also denied any history of violence.

Roger was particularly troubled by his decreased appetite, but he denied dieting or having any kind of eating disorder. He noted that he “didn’t enjoy cooking,” and his diet consisted mainly of take-out and fast food. Roger acknowledged that he should eat better and said he was not taking any vitamins or supplements.

Roger also complained of worsening memory loss and confusion: “A year or so ago, I started misplacing things: my phone, my house keys…I have trouble concentrating. I even forgot my mother’s birthday. That’s never happened before. I forgot the rent was due and had to pay a late fee.” He also noted that he was having trouble walking, which worsened over the past year or so. He denied any physical trauma. He noted that his legs “felt weaker” and his balance was “off.” He had fallen at home a few times. The patient also presented with vertical nystagmus, which was present for the past year.

Results From the Mental Status Exam

Roger was pleasant upon approach. He said he was glad he had sought admission and was “less lonely now.” He had a fresh-faced look, with good hygiene, and he maintained good eye contact. He said his mood was depressed: “a 7 or 8 on a scale of 1 to 10.” The mental status exam was normal except for some difficulty with short-term memory. He scored 22 of 30 on the mini-mental state examination, which is consistent with mild cognitive impairment. On the Montreal Cognitive Assessment Test for Dementia, Roger scored 18 of 30, which is consistent with mild dementia. The score can be influenced by factors like fatigue or sedating medications. His long-term memory was adequate.

In ascertaining his substance use history, Roger said he was a social drinker but “had managed to stop entirely over the past year.” He also noted that, up until a year ago, he drank to help with his sleeping problem, saying he “would take a couple of shots of tequila or vodka to knock me out.” He felt this strategy was “necessary to cope.” He stopped alcohol use when he had memory issues and fell at home a few times.

Insomnia, however, was still an issue. He noted that he had tried over-the-counter sleep aids, which “did nothing for me.” He volunteered that he had experimented with mushrooms while in college, which he had enjoyed, but he denied using them since then. He denied using cannabis or any other street drugs. His urine toxicology on admission was negative.

The Inpatient Unit: The Triad Comes to Light

Basic admission bloodwork results were normal. Thyroid function tests were normal. Chest X-ray was negative.

Roger was initially placed on risperidone 1 mg po BID, benztropine 0.5 mg po BID, and bupropion 75 mg po daily. He was started on desyrel 50 mg po (qHS), as needed, for the insomnia, which he said helped him sleep. He participated in many activities and groups on the unit. He was observed chatting with peers in a friendly way.

To further explore the diagnostic differential, a neurology consult was completed. The neurologist found no physical explanation for the nystagmus and ataxic gait. He concluded that both symptoms were psychogenic.

Since Roger believed he had a computed tomography (CT) scan during a prior hospitalization without any reports of abnormalities, one was not immediately completed on admission. The team requested records for the 2 prior psychiatric hospitalizations and, to be thorough, ordered a CT scan.

Similarly, an ophthalmology consult was ordered. It revealed normal healthy eyes except for the vertical nystagmus.

This triad—the combination of an eye disorder (in this case, vertical nystagmus, but it could be another ocular disturbance); a broad-based, ataxic gait; and a context of memory decrease along with mood and psychotic symptoms—was suggestive of Wernicke encephalopathy (WE) or Korsakoff psychosis.^1-3 Interestingly, this syndrome usually occurs in the context of heavy alcohol consumption, and Roger noted upon admission that he was merely a social drinker. Upon physical examination, he had no signs of chronic or advanced alcohol use, eg, broken facial capillaries (“gin blossoms”), palmar erythema, or jaundice. The liver function tests on his admission chemistry labs were elevated, but they were still within normal limits. While on the unit, he showed no signs of alcohol withdrawal.

To further explore the possibility of WE, the team chatted again with Roger about his alcohol use to ascertain more details. For instance, Roger now noted that for his long history of sleep issues, he had drunk “several glasses”—not shots—“of vodka or tequila nightly since about the age of 22 or 23.” He was now 34. Clarification of the term “several” was also pursued. Roger explained that meant “4 or 5 regular glasses; it takes that much to calm me down so I can finally sleep. I drink a lot of coffee during the day.”

Roger also admitted that this was his nightly routine, not just an occasional thing. He denied ever having any blackouts or withdrawal tremors. He explained, “I’ve always had a high tolerance for booze. It runs in my family.” He did not share these insights regarding alcohol intake at the initial interview.^4,5 He further noted, again, that he decided to stop drinking about a year ago: “I was forgetting too much stuff, oversleeping sometimes, falling at home. I didn’t want to get fired.” Roger said he “had stopped on his own,” without going to an inpatient detoxification or rehabilitation facility, and he denied any withdrawal seizures. He said he attended a few Alcoholics Anonymous meetings but did not like the vibe and stopped.

Mystery Solved—and a Treatment Plan

The head CT with contrast showed changes in the thalamus consistent with WE. There were abnormalities noted in the cerebellum consistent with ataxia. Perhaps the head CTs at the prior hospital had not been interpreted properly.² We ordered a serum thiamine (vitamin B1) level, which showed that he was severely deficient in thiamine. Based on these new findings, the criteria for WE diagnosis were met.

His loss of appetite and eating habits suggested the possibility of other vitamin deficiencies. We tested for serum vitamin B12 and vitamin D; he was severely deficient in both. This may well have contributed to his depressed mood.

To correct these vitamin deficiencies, the patient was transferred to a medicine inpatient unit. He received an intravenous (IV) bolus infusion of thiamine 500 mg 3 times daily for 2 days, then 250 mg IV daily for 5 days.² In addition, Roger was started on vitamin B12 injections and high-dose vitamin D tablets. Within about 2 weeks, all of his vitamin levels were restored to the normal range.

His vertical nystagmus stopped completely. His ataxic gait resolved. The depression lessened considerably, and his hallucinations ended.

Roger was discharged on the same psychotropic medications that he received as an inpatient: bupropion, 75 mg po qAM; risperidone, 1 mg po BID; benztropine, 0.5 mg po BID; and desyrel, 50 mg po qHS as needed for insomnia. He was also prescribed vitamin supplements of thiamine, vitamin B12, and vitamin D, as well as a therapeutic multivitamin. Finally, he received a consult with a nutritionist to address his eating habits and was referred for supportive psychotherapy to help address his depression and family issues.

Exploring WE and Korsakoff Psychosis

In general, WE is reversible with thiamine infusions. However, failure to diagnose WE can lead to a serious amnestic syndrome (Korsakoff syndrome). Korsakoff psychosis is generally irreversible. Therefore, it is extremely important that patients are diagnosed and treated as promptly as possible.^2,3

When a patient admits to social drinking, it is helpful to pinpoint the exact extent of alcohol use in terms of type of alcohol, quantity, and frequency.⁶ An assessment of a patient’s eating habits and nutritional intake (or lack thereof) can also contribute to the diagnosis and treatment of common psychiatric disorders.

A variety of evidence-based cognitive rating scales exist for WE.⁷ Heirene et al compared the neuropsychological tests used to assess alcohol-related cognitive impairment with tests that screen for alcohol-related dementia and Korsakoff syndrome (Table 1).⁷ They concluded that there is a heterogeneity in presentation and suggested using the more broad and inclusive diagnostic conceptualizations of alcohol-related cognitive impairment instead of the discrete diagnoses of Korsakoff syndrome and alcohol-related dementia.

Table 1. Testing and Assessment Options⁷

Meanwhile, Sgouros et al have pursued the development of a Thiamine Deficiency Questionnaire (TDQ) to assess thiamine deficiency in patients with severe alcohol dependence.⁸ Unfortunately, they concluded that further refinement and evaluation were needed before endorsing TDQ’s validity.

Discussion

Alcohol use (as well as the use of other nonprescribed drugs) is often underreported by patients.^4,6 According to Livingston and Callinan, “population surveys typically produce underestimates of alcohol consumption of approximately 40% to 50%.”⁴ Thus, it is essential in the initial patient interview to receive answers that are as specific as possible regarding what kind of alcohol is being consumed, how much is consumed in a drinking session, and how often the sessions occur. If the patient admits to “a couple of beers,” ask if those are 12-ounce, 16-ounce, or 24-ounce drinks. Ask about the drinking pattern: Do they drink more on weekends than on weeknights when they have to get to work the next day? Listen for words like lonely, isolated, homesick, bored, trouble sleeping, frustration, and anger, as these can be common triggers for high levels of alcohol consumption.

Table 2. Possible Causes of Wernicke Encephalopathy^9-12

Alcohol use disorder is not the only cause of WE; the culprit can be any condition that compromises the body’s access to vitamin B1 (thiamine) (Table 2).^9-12 But those are cases for another day. This one is closed.

Dr Mausner is a board-certified psychiatrist. She is on the staff of Manhattan Psychiatric Center and works in its mental health outpatient clinic. Her new book Jacob Weinberg, Musical Pioneer is available on Amazon.com.

References

1. Chandrakumar A, Bhardwaj A, ’t Jong GW. Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. J Basic Clin Physiol Pharmacol. 2018;30(2):153-162.

2. Wijnia JW, Oudman E, Bresser EL, et al. Need for early diagnosis of mental and mobility changes in Wernicke encephalopathy. Cogn Behav Neurol. 2014;27(4):215-221.

3. Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics. 2012;53(6):507-516.

4. Livingston M, Callinan S. Underreporting in alcohol surveys: whose drinking is underestimated? J Stud Alcohol Drugs. 2015;76(1):158-164.

5. Boniface S, Shelton N. How is alcohol consumption affected if we account for under-reporting? a hypothetical scenario. Eur J Public Health. 2013;23(6):1076-1081.

6. Boniface S, Kneale J, Shelton N. Drinking pattern is more strongly associated with under-reporting of alcohol consumption than socio-demographic factors: evidence from a mixed-methods study. BMC Public Health. 2014;14:1297.

7. Heirene R, John B, Roderique-Davies G. Identification and evaluation of neuropsychological tools used in the assessment of alcohol-related cognitive impairment: a systematic review. Front Psychol. 2018;9:2618.

8. Sgouros X, Baines M, Bloor RN, et al. Evaluation of a clinical screening instrument to identify states of thiamine deficiency in inpatients with severe alcohol dependence syndrome. Alcohol Alcohol. 2004;39(3):227-232.

9. Choi EY, Gomes WA, Haigentz M Jr, Graber JJ. Association between malignancy and non-alcoholic Wernicke’s encephalopathy: a case report and literature review. Neurooncol Pract. 2016;3(3):196-207.

10. Hutcheon DA. Malnutrition-induced Wernicke’s encephalopathy following a water-only fasting diet. Nutr Clin Pract. 2015;30(1):92-99.

11. Shible AA, Ramadurai D, Gergen D, Reynolds PM. Dry beriberi due to thiamine deficiency associated with peripheral neuropathy and Wernicke’s encephalopathy mimicking Guillain-Barré syndrome: a case report and review of the literature. Am J Case Rep. 2019;20:330-334.

12. Togay-Işikay C, Yiğit A, Mutluer N. Wernicke’s encephalopathy due to hyperemesis gravidarum: an under-recognised condition. Aust N Z J Obstet Gynaecol. 2001;41(4):453-456.❒