Catatonia in Duchenne Muscular Dystrophy: An Illustrative Case Report and Review of the Literature

Duchenne muscular dystrophy (DMD) is a genetic disorder that causes progressive muscular weakness as a result of mutations in the DMD gene. Dystrophin, the protein encoded by the DMD gene, is necessary for skeletal muscle integrity; however, it is also found in the brain, where it is implicated in neural functioning. Patients with DMD are more likely to be diagnosed with an array of neuropsychiatric illnesses, such as attention-deficit hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, and major depressive disorder (1).

Catatonia is a psychomotor syndrome characterized by changes in behavior, affect, and movement. Susceptibility to catatonia varies across patients, and those at highest risk include individuals with underlying neuropathology, medical frailty, and underlying psychiatric illness (2). In addition to arising secondary to medication use or withdrawal, the most common etiologies of catatonia include mood disorders, psychosis with or without exposure to antipsychotics, neurological diseases, and metabolic disorders (2). Although the pathophysiology of catatonia is not fully understood, contemporary models have converged on frontal lobe dysfunction related to aberrant dopaminergic and gamma-aminobutyric acid (GABA)-ergic tone (2, 3).

Here, we describe a case of catatonia presenting in a patient with DMD with no psychiatric history and no notable changes from his baseline state of health before hospitalization. A review of the literature revealed that there has been one other reported case describing catatonia in a patient with DMD; however, that patient was critically ill and required care in the intensive care unit prior to a diagnosis of catatonia (4).

Case Presentation

A 29-year-old man with a medical history of DMD, complicated by cardiomyopathy and restrictive lung disease, presented to the emergency department with paranoia, auditory and visual hallucinations, delusions, and poor oral intake that he had been experiencing for 1 week. Per parent report at bedside, the patient had previously been at his baseline state of health. He presented for evaluation at an outside emergency department 1 week earlier and had a negative preliminary infectious workup, which included urinalysis, chest X-ray, and COVID-19 test. His symptoms had not resolved at the follow-up, prompting his primary care physician to recommend presentation to a tertiary care facility for comprehensive evaluation.

The patient was a high school graduate. He did not have any recorded learning disabilities, any previous psychiatric admissions, or history of taking psychotropic medications. At baseline, he retained some limited ability to use his hands. His independent activities included using his cell phone in his lap and using his electric wheelchair, although the latter activity had become very challenging in the previous months. Otherwise, he was dependent on family members for all other activities of daily living. Despite these challenging circumstances, the patient had been without signs of depression before his change in mental status.

In the emergency department, he was afebrile, with baseline tachycardia and tachypnea. Physical examination was notable for prominent muscle wasting in all extremities with a resultant inability to move against gravity. He made references to shooters in the hospital, asked to confirm the identity of people in the room, and conversed with unseen others about bizarre topics. When food or medication was brought to his lips, he allowed it to be placed in his mouth before spitting it out. Staring and verbigeration was observed. Echophenomenon was reportedly prominent over the past several days, and the grasp reflex was present. His initial Bush-Francis Catatonia Rating Scale (BFCRS) score was 11 (higher scores denote greater symptom severity) (5).

His initial laboratory examination was notable for mild leukocytosis. An arterial blood gas test revealed mild chronic hypercarbia consistent with his baseline levels. Increased respiratory support with bilevel positive airway pressure therapy yielded no improvement in his mentation. HIV and syphilis tests, hepatitis panel, cryptococcal antigen screening, blood cultures, and urine cultures were negative. Electrocardiogram and echocardiogram results were unchanged from previous evaluations. Head CT and MRI were unremarkable, and urine toxicology was negative. The patient was admitted to inpatient neurology service for continued workup that included a lumbar puncture with normal cerebrospinal fluid (CSF) levels (nucleated cells, 0; glucose, 90; protein, 22), negative herpes simplex virus polymerase chain reaction (PCR) test, negative meningitis panel, and negative cytomegalovirus PCR test as well as prolonged electroencephalogram monitoring with no epileptiform activity. CSF was obtained for an autoimmune encephalitis panel, a send-out laboratory test for which the availability of results can take up to several weeks. To avoid delay in treatment, empiric treatment of autoimmune encephalitis was initiated on the basis of clinical suspicion. The patient was placed on high-dose steroids with a plan to initiate plasma exchange and continue the search for the source of presumed autoantibodies.

Following lorazepam challenge, the patient’s mental status improved remarkably, and the BFCRS score was 0. He apologized for his previously disinhibited behavior, ate a snack, and asked relevant questions about his care.

A full-body CT scan and testicular ultrasound were obtained to evaluate for teratoma, both of which failed to reveal abnormalities. The patient underwent five rounds of plasma exchange and steroids with no improvement. A follow-up brain MRI on day 11 was unchanged from admission. Both serum and CSF autoimmune panels came back negative (Table 1), and a heavy metals screen was negative.

The patient continued to exhibit catatonic features (BFCRS scores from 3 to 8) despite escalating doses of lorazepam. His maximum daily dose of lorazepam reached 16 mg, in combination with nightly memantine 10 mg and nightly zolpidem 10 mg. Because of signs of delirium in the context of suspected benzodiazepine intoxication, a 2-mg dose reduction of benzodiazepines was attempted. This yielded tachycardia to 150 beats per minute, an increase from his baseline heart rate of 120, as well as fever and worsening mentation.

Due to intractability of the patient’s catatonia and concerns for progression to malignant catatonia, electroconvulsive therapy (ECT) was considered. Given the need for tracheostomy, ECT was declined by the family in accordance with the patient’s wishes. He was discharged to home hospice and died at home within 1 week of discharge.

Discussion

Catatonia presenting in a patient with DMD has rarely been described in the literature. Our case is unique in that the patient had no psychiatric history and no notable changes from his baseline physical health before hospitalization. This distinct presentation provides an opportunity to consider a potential association between DMD and catatonia.

The brains of patients with DMD have biochemical, histological, and anatomical differences when compared with those of healthy control subjects (6–8). At a gross level, patients with DMD exhibit cerebral atrophy that possibly worsens throughout the lifespan (6). At the synaptic level, dystrophin isomers play an integral role in clustering of GABA receptors in the prefrontal cortex (7, 8). Dysfunctional neural dystrophin isoforms have been posited to be responsible for the high prevalence of neuropsychiatric comorbidity observed among patients with DMD (9, 10). The present case offers a hypothetical link between neural dystrophin dysfunction and catatonia via GABA-ergic dysfunction in the prefrontal cortex. In this case, in the absence of obvious medical and psychiatric etiology of the patient’s catatonia, we suggest that the pathophysiology of the patient’s catatonia may have been linked to dystrophin dysfunction and the resulting neural dystrophin isoforms’ interaction with GABA_A receptors in the prefrontal cortex.

The differential diagnosis for our patient included neurological and psychiatric disorders, such as autoimmune encephalitis, frontal lobe seizures, nonconvulsive status epilepticus, drug intoxication or withdrawal, delirium, and atypical presentation of primary affective or psychotic disorders. Given the acute timeline, lack of previous psychiatric history, and lack of behavioral changes in the weeks leading up to the patient’s decompensation, a primary affective or psychotic disorder was felt to be unlikely.

Despite initial improvement following the lorazepam challenge, benzodiazepine monotherapy proved to be insufficient for symptom control. When benzodiazepine therapy is insufficient, pharmacological adjuncts can be offered. Memantine and zolpidem have been shown to be effective adjuncts in the treatment of catatonia, which is thought to be a result of their N-methyl-d-aspartate receptor antagonism and positive allosteric effect on GABA_A receptors, respectively (11, 12). The patient was started on nightly memantine 10 mg and nightly zolpidem 10 mg. He continued to decompensate despite empiric treatment of autoimmune encephalitis. When his CSF autoantibody screen was negative, clinical suspicion of autoimmune encephalitis receded.

Patients who are unresponsive to pharmacological intervention should be offered ECT as a next step. Given our patient’s tenuous cardiopulmonary status, a tracheostomy was necessary for initiation of an index course of ECT. He had a clear historical preference to forgo tracheostomy. His wishes were respected, and he was discharged to home hospice.

Conclusions

This case provides an opportunity to consider neuropsychiatric comorbidity in DMD in relation to dysfunction in neural dystrophin gene products, which is supported by neuroimaging and histological findings (6–10, 13–15). This case also highlights the challenges related to diagnosing catatonia in the absence of a reliable psychomotor examination. We recommend that providers who encounter a high volume of patients with catatonia (internists, psychiatrists, and neurologists, among others) consider catatonia early and have a low threshold for performing a lorazepam challenge among patients with unreliable psychomotor examinations.

We propose that our patient’s catatonia was a manifestation of end-stage DMD. Further research on this topic is necessary to fully elucidate the connection between DMD and catatonia. Although no modified catatonia rating scales have been developed for patients with DMD, Hauptman et al. (16) provide guidance in assessing catatonic regression from baseline among patients with autism spectrum disorders, which may be of conceptual interest to clinicians.

Key Points/Clinical Pearls