Paraneoplastic Limbic Encephalitis
Paraneoplastic limbic encephalitis (PLE) is a rare neurological consequence of certain cancers. Although PLE most commonly occurs in patients with small cell lung cancer, the condition has also been reported (though less frequently) in cases of esophageal adenocarcinoma, ovarian teratoma, metastatic breast cancer, and germ cell testicular cancer.5 This disease overlaps substantially with anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis. Moreover, PLE can present initially with prominent neuropsychiatric symptoms such as confusion, cognitive problems, behavioral changes, irritability, depression, or frank psychosis with hallucinations. Paraneoplastic limbic encephalitis can occur early in the course of cancer—often before other systemic signs appear—and its significance is often only recognized in retrospect or postmortem. A higher index of suspicion for the disorder may lead to earlier detection of treatable cancers.
Malignant Meningitis
Malignant meningitis is the metastatic spread of a primary solid tumor to the leptomeninges. It can present as a wide variety of neuropsychiatric complaints, including depression, anxiety, disorientation, and paranoia. Diagnosis can often be made through lumbar puncture. Malignant meningitis should be considered in the differential diagnosis of new psychiatric symptoms in a patient with a history of cancer—even in the absence of focal neurological deficits or meningeal signs.6
Pancreatic Insulinoma
Pancreatic insulinoma is a rare, potentially curable endocrine tumor that can present initially with vague psychiatric complaints such as irrational behavior, confusion, depression, or anxiety. In up to 64% of patients, insulinomas are misdiagnosed as primary neurological or psychiatric disease, which can delay potentially curative surgery—sometimes for years.7 The EP should suspect pancreatic insulinoma in any patient who presents with psychiatric symptoms and unexplained episodes of hypoglycemia.7
Cardiac Disease
Transient Left Ventricular Apical Ballooning Syndrome
Transient left ventricular apical ballooning syndrome (TLVABS), first identified in Japan as Takotsubo syndrome, has more recently been recognized worldwide as overlapping with the classic broken heart syndrome. In postmenopausal women, TLVABS appears to follow a catecholamine surge triggered by extreme emotional stress, resulting in an acute coronary artery spasm. Researchers have hypothesized that there may be a link between TLVABS and dissociative amnesia, which is also thought to result from a catecholamine surge in response to emotional stress.8
Nutritional Deficiencies
Wernicke/Korsakoff Syndrome and Thiamine Deficiency
Wernicke encephalopathy and Korsakoff syndrome (WKS) represent a spectrum of neurodegenerative disorders caused by thiamine deficiency. The condition typically occurs in malnourished alcoholic patients, manifesting as a triad of mental status changes, ophthalmoplegia, and ataxia. Recent research has suggested that WKS is more common than previously thought, is not confined exclusively to alcoholic patients, is unlikely to present with the full classic triad, and is typically only diagnosed postmortem.9
Nonalcoholic WKS tends to occur in younger female patients with a wide array of conditions that affect nutrition (eg, gastrointestinal malignancy, bariatric surgery, hyperemesis gravidarum, anorexia nervosa).9 In a patient with chronic alcoholism, application of the Caine criteria (any two of the following findings: ophthalmoplegia, ataxia, even mild memory impairment or confusion without another cause, evidence of malnutrition) has been shown to be more sensitive and specific than the classic triad.10
Subacute Combined Degeneration
Patients with subacute combined degeneration and extrapyramidal symptoms due to B12 (cobalamin) deficiency are well documented. However, patients with B12 deficiency can also present with mood disorders, acute psychosis, psychotic depression, or paranoid hallucinations. The EP should always consider vitamin B12 deficiency as an important, reversible cause of altered mental status—even in the absence of megaloblastic anemia—especially in patients with celiac disease or anorexia nervosa, and in teenagers and those who are vegans/vegetarians.11
Zinc/Vitamin D Deficiency
Zinc and vitamin D deficiency are both highly prevalent in geriatric patients and have been associated with a range of psychiatric complaints, including depressive disorders, bipolar disorder, and psychotic episodes. Though the neurodevelopmental effects of long-term deficiency of these nutrients are well documented in pediatric patients, the role and relationship to acute psychiatric complaints in elderly patients remain unclear.12,13
Endocrine Disorders
Hypothyroidism
Hypothyroidism is a commonly encountered endocrine disruption that classically presents with fatigue, cold insensitivity, weight gain, and thinning hair. Thyroid dysfunction can result in various neuropsychiatric presentations, including mood disorders, cognitive impairment, and exacerbation of underlying psychiatric disorders. Though rare, primary hypothyroidism can present as mania, psychosis, and auditory or visual hallucinations, a phenomenon termed “myxedema madness.” Myxedema madness typically occurs in older women, but has also been described in adolescents and as a postoperative complication of thyroidectomy.14
Hyperthyroidism
Hyperthyroidism classically presents with tachycardia, nervousness or anxiety, heat insensitivity, and weight loss despite increased appetite. Involvement of the CNS in thyrotoxicosis is rare, but when present, it is a significant predictor of mortality. Neuropsychiatric presentations of hyperthyroidism or thyroid storm vary widely, and have been reported to include psychosis, catatonia, auditory hallucinations, delusional parasitosis, new-onset sleepwalking, dissociative disorder, and suicide attempts.15