TREATMENT Methylphenidate and a safety plan
On Day 11 of hospitalization, Mr. G is started on methylphenidate, 10 mg in the morning and 5 mg in the afternoon. After starting methylphenidate, he sustains more regular wakefulness, with improved thought organization, engagement, and fewer disruptive behaviors. He receives infrequent, as-needed doses of olanzapine, and by Day 14, he returns to his baseline behavior and cognition.
A safety plan is created for the family to address worsening symptoms or future episodes. The safety plan is developed with Mr. G and input from his family. It is to be administered in all settings and we particularly emphasized using it in the school setting, where staff may not be familiar with KLS. The safety plan involves a description of KLS, its symptoms, the risks for hypersomnolence, hypersexuality, and psychotic symptoms or behavioral dysregulation. It stresses close supervision of Mr. G, not allowing him to be unsupervised or unchaperoned on school trips or other outings, and lethal means restriction. It outlines a detailed plan if Mr. G’s behavior decompensates or escalates, including a step-wise approach to engaging psychological interventions and mental health resources, and securing crisis services as needed.
On Day 15, he is discharged to home in stable condition with outpatient mental health follow-up and continues to take the prescribed methylphenidate.
The authors’ observations
Management of KLS is primarily supportive. Stimulants may help reduce hypersomnia, impulsivity, and inattention early in the disease course.1 However, in a systematic review, 89% of patients with KLS who received methylphenidate experienced worsening or no improvement, and 11% showed only partial improvement.2 Amantadine was more promising, with 29% of patients with KLS showing partial benefit and 12% showing significant benefit.2 Multiple other pharmacologic agents have been described with varying efficacy, including lithium, valproate, risperidone, bupropion, and immunoglobulins.2 Furthermore, lithium and valproate have been suggested to be helpful in preventing recurrences in some cases.6
The circumstances surrounding Mr. G’s symptom onset are unclear and may have been multifactorial. It is possible that his prior EBV infection was a trigger for this KLS-associated episode, as EBV is a known precipitant for KLS episodes.3 Mr. G’s history of cannabis use may also have served as an early trigger for KLS.3
This case highlights the importance of multidisciplinary collaboration in a diagnostically challenging case. It emphasizes the need for a broad differential and the importance of challenging a previous diagnosis in the face of mounting evidence to the contrary. In this case, the patient’s history of irritability, aggression, and cannabis use resulted in multiple clinicians misattributing his symptoms to substance use or a primary psychiatric disorder. However, given his symptom acuity, progression, and the lack of findings on diagnostic evaluation to explain his presentation, these initial diagnoses did not explain the severity, nature, or duration of his symptoms. Keeping KLS in the differential is particularly important for patients with a prior history of psychiatric illness or substance use, because these patients are at higher risk for misattribution of symptoms to pre-existing psychiatric illness. Evolution of symptoms, a negative diagnostic evaluation, and maintaining a broad differential resulted in eventually reaching the final diagnosis of KLS and development of a longitudinal management plan.
While further work must be done to clearly define the pharmacologic approach to acute management of KLS episodes, nonpharmacologic aspects of care must not be neglected. Behavioral planning, adjustment of the environment, engagement with schools/community supports, and family education are valuable tools for facilitating the patient’s de-escalation, avoiding unneeded polypharmacy, reducing anxieties, and safeguarding the patient from unnecessary harm.7 Clinicians can support their patients’ transitions back into the community by ensuring careful outpatient follow-up for symptom monitoring and by communicating with patients’ schools and employers.
OUTCOME Asymptomatic; no recurrence of symptoms
Forty-six days after his symptoms began and 31 days after hospital discharge, Mr. G is asymptomatic with no recurrence of symptoms.
Bottom Line
Kleine-Levin syndrome (KLS) is a rare, often-overlooked condition that should be considered in the differential diagnosis for patients who present with hypersomnolence and altered mental status without a clear etiology. Rapid recognition of KLS can prevent misattribution of symptoms, unnecessary treatment, and missed opportunities for care.