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A 92-year-old woman presents for admission to a psychiatric hospital, 3 months after being diagnosed with catatonia. Her symptoms include stupor and waxy flexibility (i.e., resisting passive movement); she is nonverbal, resistant to commands (i.e., negativism), and agitated.

The patient has no medical or family history of psychiatric or neurodegenerative diseases. Notably, she was employed as a dietitian for most of her adult life, until she retired at the age of 80.

She has been transferred for admission to the psychiatric hospital after treatment with lorazepam (Ativan, up to 6 mg/d) for 1 month failed to improve her symptoms. Her recent medical history includes a hospitalization for heat stroke at the age of 88, followed by frequent hospital visits for insomnia.

One year prior to the current admission, she had been prescribed ramelteon (Rozerem) to treat her insomnia. Clinicians had ruled out potential dementia based on the patient's Mini-Mental State Examination (MMSE) score of 21/30 at the age of 91 as well as her ability to perform everyday functions – including going shopping and taking a walk – unassisted. Three months later, the patient developed symptoms of catatonia.

On admission, testing on the Bush-Francis Catatonia Rating Scale (BFCRS) results in a score of 37/69. Findings of electroencephalography and laboratory blood tests are unremarkable. Brain magnetic resonance imaging reveals diffuse mild cerebral atrophy and leukoaraiosis (Figure 1A).

Given the reported effectiveness of amantadine for catatonia, the patient receives amantadine 100 mg/d via a nasogastric tube to treat her muscle rigidity, beginning on day 2. A week later, on day 9, clinicians note a partial response; the patient's BFCRS score is 25/69. Thus, they slowly begin to increase her dose of amantadine to 200 mg/d.

On day 15, the patient's catatonia is almost resolved, with a score of 4/69 on the BFCRS. Subsequent testing reveals evidence of memory loss, impaired visuospatial function, and disorientation; her MMSE score is 13/30.

In an effort to determine the cause of the patient's cognitive impairment, clinicians perform imaging studies for dementia with Lewy bodies (DLB) disease biomarkers. They note decreased heart-to-mediastinum ratios of 123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy (early 1.31, delayed 1.00, cutoff 2.20; Figure 1B above). Single-photon emission computed tomography with iodine 123-N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta- (4-iodophenyl) nortropane (123I-FP-CIT SPECT) shows reduced dopamine transporter availability in the bilateral striatum (Figure 1C above).

Carbon 11-Pittsburgh compound B-positron emission tomography reveals no sign of amyloid deposition. Despite the absence of any core clinical features of DLB, she has two indicative biomarkers on 123I-MIBG myocardial scintigraphy and 123I-FP-CIT SPECT, allowing a diagnosis of possible DLB disease according to the .

On day 29, the patient is referred to the previous psychiatric hospital for rehabilitation. About 6 months after discharge, she begins having visual hallucinations and showing symptoms of parkinsonism, such as bradykinesia and dysphagia; these core clinical features of DLB allowed clinicians to confirm the diagnosis of DLB.

Discussion

Clinicians reporting this of a woman with DLB-related catatonia but no core clinical features of DLB note that this is the first report of catatonia as an initial symptom of DLB disease, a diagnosis confirmed using biomarkers.

They note that this patient's catatonia may have resulted from DLB-related dysregulation of the dopaminergic system, given its presumed role in the pathophysiology of catatonia. A similar mechanism could be involved in catatonia that occurs in Parkinson's disease, given that it is also a Lewy body disease. Still, authors note that, theoretically, catatonia would develop after dopaminergic system dysfunction causes DLB, not prior to the dementia.

Authors point out that there have been very few reports regarding catatonia in DLB, perhaps due to neurologists' of catatonia, since DLB usually presents with extrapyramidal signs. They propose a second explanation may be that "in addition to dysfunction of the dopaminergic systems, other mechanisms may increase the risk of developing catatonia in DLB."

They note theories suggesting that catatonia may occur due to concurrent hyperactivity of the N-methyl-d-aspartate (NMDA) receptor and dysfunction of the dopaminergic system in the striato-cortical or the cortico-cortical pathways.

This patient's DLB-related catatonia responded well to amantadine, a drug that has both NMDA receptor antagonistic and dopamine receptor agonistic properties, the authors noted, suggesting involvement of both dopaminergic and glutamatergic systems in this patient's catatonia. "Furthermore, the rarity of catatonia in DLB may be explained by it emerging under the situation of NMDA hyperactivity together with dopaminergic hypofunction," authors write.

Catatonia may be associated with a variety of neuropsychiatric disorders, including mood disorders, psychosis, drug intoxication, and neurodegenerative disorders. Standard treatment is benzodiazepines such as lorazepam and diazepam, with consideration of antipsychotics, NMDA receptor antagonists (amantadine or memantine [Namenda]), nonbenzodiazepine hypnotic zolpidem, or electroconvulsive therapy in cases of poor response.

"DLB is associated with loss of dopaminergic neurons in the substantia nigra and is characterized by cognitive impairment, visual hallucinations, parkinsonism, and a marked sensitivity to antipsychotics," authors noted. Thus treatment with antipsychotics is not recommended, they write, referring to their recent report of a neuroleptic malignant syndrome that developed in a DLB patient after treatment with the atypical antipsychotic drug, quetiapine.

Similarly, electroconvulsive therapy is not advised for elderly patients due to its potential to result in cognitive impairment. Therefore, amantadine treatment may be the most rational choice for catatonia in DLB that is not responding to benzodiazepines, authors write. And as with amantadine, it is also important to investigate whether memantine and nonbenzodiazepine hypnotic zolpidem are effective for benzodiazepine-resistant catatonia in DLB.

In addition to the core symptoms described previously, there is growing awareness that early symptoms of DLB may include visual hallucinations, depression, and REM sleep behavior disorder, clinicians note. They cite a recent 234-patient showing that DLB-related symptoms differed between men and women at diagnosis. Almost half of the women initially presented with psychiatric symptoms, with significantly more women than men presenting with auditory hallucinations. In contrast, men had a significantly higher rate of rapid eye movement sleep behaviour disorder, parkinsonism, hyposmia, and syncope than female patients.

Indicative biomarkers of DLB on 123I-MIBG myocardial scintigraphy and dopamine transporter imaging are central to diagnosing DLB during the prodromal stage.

Case authors conclude by cautioning that in the absence of the core clinical features to aid , "development of catatonia should be considered an initial symptom of DLB. Moreover, given the plausible pathophysiology of benzodiazepine-resistant catatonia in DLB and the adverse effects of alternative treatments, amantadine treatment may be the most rational choice for the condition."

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