Case description

A man in his late 30s with metastatic melanoma involving bone, lungs, brain, and leptomeninges was admitted with progressive weakness, reduced oral intake, headache, nausea, and altered mental status. His neurologic history included leptomeningeal disease complicated by hydrocephalus requiring ventriculoperitoneal shunting and seizures treated with brivaracetam. He had recently received proton craniospinal irradiation and remained exposed to corticosteroids and cancer-directed therapy. Shortly before admission, he had been fully oriented, fluent, attentive, independently ambulatory, and independent in activities of daily living.

During hospitalization, his mental status fluctuated substantially. He was variably disoriented, inattentive, somnolent, and unable to provide a coherent history. At other times, he refused food, medications, care, or safety recommendations and required repeated prompting. Neurologic evaluation included electroencephalography and serial neuroradiologic studies. Leptomeningeal disease, possible shunt dysfunction, irradiation, corticosteroids, seizures, acute illness, poor intake, sleep disruption, and centrally acting medications remained plausible contributors. The evolving formulation was toxic-neurologic encephalopathy with delirium.

Psychiatry was consulted after reduced speech, and movement and episodic waxy flexibility were observed. On the initial Bush-Francis Catatonia Rating Scale (BFCRS) examination, immobility, mutism, staring, and withdrawal each scored 1, and waxy flexibility scored 3, for a total of 7. A 2-mg intravenous lorazepam challenge was administered. He fell asleep within 35 minutes, preventing a meaningful immediate reassessment. Four hours after intravenous lorazepam administration, the score was 1 for mutism alone; arousal remained somewhat somnolent. Other examinations documented variable mutism, repetitive hand movements, perseveration, echolalia or verbigeration, stereotypy, negativism, resistance, automatic obedience, and ambitendency. The clustered findings raised concern for catatonic features, but their prominence varied with arousal. Concurrent fluctuations in attention, orientation, and wakefulness supported delirium within a broader encephalopathy. There was no sustained fever, severe rigidity, autonomic instability, or other evidence of malignant catatonia.

The patient was placed on a scheduled Ativan dose of 1 mg twice daily after this trial described above. Scheduled intravenous lorazepam was then progressively reduced by total daily dose from 2 mg to 1.5 mg, 1 mg, and 0.75 mg. When twice-daily dosing was used, doses were given at 1 PM and 8 PM; morning administration was avoided to prevent confusion with the antiseizure-medication schedule and avoid comorbid oversedation. Transient increases in movement, speech, and walking occurred, but somnolence, disorientation, concurrent care, and spontaneous fluctuation prevented causal attribution. The dose was briefly returned to 1 mg total daily. Severe agitation subsequently emerged, and standing lorazepam was stopped rather than interpreted as beneficial on the basis of the lower BFCRS score alone.

Over subsequent days, catatonic signs became less sustained, while impaired attention, fluctuating arousal, somnolence, and disorientation remained prominent. This course supported the evolving impression of a broader encephalopathy with delirium and intermittent early catatonic features; it did not exclude possible catatonia early in the admission.

The syndrome later included recurrent late-day agitation, line-pulling, and behavioral rapid-response activations; 2 episodes resulted in staff injury. Scheduled haloperidol was introduced for behavioral safety rather than a primary psychotic disorder and adjusted to 3 mg orally at 4 PM and 10 PM, with intravenous haloperidol reserved for severe, nonredirectable agitation. Documented evening agitation improved after this change. No extrapyramidal symptoms, rigidity, oversedation, or QTc change occurred. Pain was evaluated as a potentially modifiable contributor.

Repeat magnetic resonance imaging was limited by intolerance but demonstrated persistent leptomeningeal abnormality on available sequences. During a multidisciplinary family meeting, Neurology identified leptomeningeal disease as the most likely driver of his altered mental status and proton craniospinal irradiation as the next most likely contributor; neither was expected to improve with medical optimization. His wife initially favored additional cancer-directed treatment but, after discussion of his functional status and prognosis, considered care at home with an emphasis on comfort. She asked that corticosteroids and psychiatric medications be reduced when feasible to preserve wakefulness, mobility, nutrition, and communication. The team also explained that uncontrolled agitation could make home care unsafe.

On the final documented evening, Supportive Care collaborated on a trial of oral medication while his wife remained overnight. With her present, no further episode of agitation was documented. He remained pleasantly confused, oriented to self and partly to place, and was not oversedated. The calm night supported a plan for discharge home with hospice, but the transition remained pending because of medical-insurance barriers.