What are the possible differential diagnoses for a patient presenting with frequent yawning and tearing?

Differential Diagnosis of Frequent Yawning and Tearing

Frequent yawning with tearing should prompt immediate evaluation for opioid withdrawal, followed by systematic assessment for neurological, iatrogenic, and metabolic causes, as these presentations can indicate serious underlying pathology requiring urgent intervention.

Immediate Life-Threatening Considerations

Opioid Withdrawal Syndrome

• Frequent yawning (≥3 yawns per 15 minutes) combined with tearing is a cardinal feature of opioid withdrawal and should be assessed using the Clinical Opiate Withdrawal Scale (COWS). 1
• The COWS assigns 0 points for no yawning, 2 points for yawning 3+ times during assessment, and 4 points for yawning several times per minute. 1
• Tearing is scored separately: 0 for not present, 1 for nasal stuffiness or moist eyes, 2 for nose running or tearing, and 3 for tears streaming down cheeks. 1
• Other accompanying features include sweating, restlessness, pupil dilation, bone/joint aches, GI upset, and elevated pulse rate—all of which increase the likelihood of withdrawal. 1
• A total COWS score of 5-12 indicates mild withdrawal, 13-24 moderate, 25-36 moderately severe, and >36 severe withdrawal requiring immediate intervention. 1

Neurological Causes

Pathological Yawning from Structural Brain Lesions

• Pathological yawning is defined as salvos of 10-20 successive yawns or >100 yawns per day, far exceeding the physiological 3 yawns per 15 minutes threshold. 2, 3
• Stroke, particularly involving the brainstem, hypothalamus, or insula, can cause pathological yawning through disruption of the yawning network. 2, 4
• Brain tumors, especially those affecting the hypothalamic paraventricular nucleus or brainstem motor pattern generators, should be considered. 2, 3
• Intracranial hypertension from any cause (mass lesion, hydrocephalus, pseudotumor cerebri) can manifest with pathological yawning. 2, 4
• Chiari malformation type I may present with excessive yawning as an early sign. 4
• Multiple sclerosis plaques affecting the yawning network can cause this symptom. 4

Neurodegenerative and Movement Disorders

• Parkinson's disease and parkinsonism can present with altered yawning patterns due to dopaminergic dysfunction. 5, 4
• Amyotrophic lateral sclerosis (ALS) may cause pathological yawning as part of bulbar dysfunction. 2, 4
• Parakinesia brachialis oscitans (involuntary arm movement during yawning in hemiplegic patients) indicates corticospinal tract involvement. 4

Epilepsy

• Yawning can occur as an ictal or post-ictal phenomenon in temporal lobe epilepsy. 4

Iatrogenic and Pharmacological Causes

Medication-Induced Yawning

• Selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacological cause of excessive yawning. 6, 5
• Dopaminergic medications can paradoxically cause yawning through complex neurotransmitter interactions. 5
• The mechanism involves dopamine activation of oxytocin in the paraventricular nucleus, which then activates cholinergic transmission in the hippocampus, ultimately inducing yawning via muscarinic receptors. 5
• Other neurotransmitters modulating yawning include nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, and opioid peptides. 5

Metabolic and Systemic Causes

Chronic Disease and Anemia

• Chronic disease anemia from underlying malignancy (such as endometrial carcinoma) can present with excessive yawning, palpitations, and shortness of breath. 6
• This presentation can be misattributed to psychiatric disease alone, leading to delayed diagnosis of serious underlying pathology. 6

Infectious Causes

• Various infections affecting the central nervous system can cause pathological yawning. 5, 2

Psychiatric Considerations

Anxiety and Psychiatric Disorders

• Generalized anxiety disorder can be associated with excessive yawning, but organic causes must be excluded first. 6
• Schizophrenia and autism spectrum disorders rarely present with altered yawning patterns. 4
• Medical stigmatization can lead to misdiagnosis when psychiatric symptoms mask underlying organic pathology. 6

Diagnostic Algorithm

Initial Assessment

• Obtain detailed medication history, focusing on opioid use, SSRIs, and dopaminergic agents. 1, 6, 5
• Perform COWS assessment if opioid withdrawal is suspected, scoring yawning frequency and tearing severity. 1
• Document yawning frequency: physiological (<3 per 15 minutes) versus pathological (salvos of 10-20 or >100 per day). 2, 3
• Assess for accompanying neurological symptoms: headache, focal deficits, altered consciousness, seizures. 2, 4

Laboratory Evaluation

• Complete blood count to assess for anemia. 6
• Basic metabolic panel and renal function. 6
• Consider thyroid function tests for endocrinopathies. 5

Neuroimaging Indications

• Brain MRI with and without contrast is indicated for pathological yawning (≥3 yawns per 15 minutes without obvious cause) to evaluate for stroke, tumor, demyelination, or structural abnormalities. 2, 3
• Urgent imaging is required if accompanied by headache, focal neurological signs, or altered mental status. 2, 4

Critical Pitfalls to Avoid

• Do not attribute excessive yawning and tearing solely to psychiatric disease without excluding opioid withdrawal, neurological lesions, and systemic illness. 6, 2
• Do not dismiss SSRI-induced yawning as benign without considering dose reduction or medication change if it impairs quality of life. 6, 5
• Do not delay neuroimaging in patients with pathological yawning patterns, as this may represent serious intracranial pathology. 2, 3
• Medical stigmatization of psychiatric patients can lead to missed diagnoses of serious organic disease such as malignancy. 6