Introduction

Catatonia is a psychomotor syndrome characterized by motor signs associated with mood, behavior, and thought disorders. This syndrome can occur in the context of different psychiatric conditions including affective, psychotic, and neurodevelopmental disorders, but may also be diagnosed in association with non-psychiatric conditions, including neurological, autoimmune, endocrine, and infective diseases [1]. Motor alterations that characterize catatonia typically have an acute onset and are often associated with mood changes. Stupor, mutism, negativism, rigidity, posturing, and staring are prominent motor signs [2]. Despite the differential diagnosis can be challenging, catatonia is a syndrome with a good prognosis if early identified and treated. The diagnosis can be verified by rapid relief with the intravenous administration of benzodiazepines. The choice of treatment, whether benzodiazepines or electroconvulsive therapy (ECT), is determined by the severity of the illness, the presence of fever, and the degree of autonomic instability. The use of neuroleptics can be potentially harmful and should be avoided until catatonic signs are present [3, 4]. Catatonia may be diagnosed as a specifier that better characterize underlying mental disorders or specific medical conditions based on the presence of at least three signs from the following list: stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerisms, stereotypies, agitation, grimacing, echolalia, and echopraxia [5]. Since all catatonic signs pertain to the psychomotor domain, any comorbid syndrome associated with motor alterations may complicate the diagnosis of catatonia.

Parkinson’s disease (PD), historically defined as a movement disorder, is now considered the prototypical neuropsychiatric condition, in which motor signs, such as tremors, rigidity, and bradykinesia, occur together with cognitive and neuropsychiatric features [6]. Depression [7], bipolar disorder [8, 9], psychosis [10], anxiety [11], impulse control disorders [12], apathy [13], and sleep disturbances [14] can frequently and significantly impact the course of PD. Despite the high psychiatric comorbidity reported in PD patients, few cases of catatonia have been reported in the literature [15–18]. Given the overlapping manifestations of catatonia and PD, especially the akinetic type, the differential diagnosis may be difficult in some cases. In severe PD patients, in fact, catatonia is frequently misdiagnosed and overlooked. However, acute akinesia, a condition that may be difficult to distinguish from catatonia, has been described in patients with PD [19]. Acute akinesia, indeed, is considered a rare complication of PD, which can occur as a result of infections, traumas, surgery, or gastrointestinal tract diseases. As in the case of malignant catatonia, the clinical picture is characterized by a sudden deterioration in motor performance persisting for 48 h or more, despite treatment, and resulting in a hypertonic-akinetic state usually associated with increases of body temperature and muscular damage, as evidenced by increments of creatine phosphokinase and myoglobin [19].

Despite symptoms of catatonia and PD may appear clinically similar, they are likely to stem from different pathological backgrounds. On one hand, catatonia has been hypothesized to reflect “top-down” dysfunction of the cortico-striatal-thalamic-cortical loop, involving both gamma-aminobutyric acid (GABA)ergic, glutamatergic, and dopaminergic systems [20]. In PD, instead, motor symptoms result from dopaminergic-mediated deficits in the striatum that lead to alterations in “bottom-up modulation” of the premotor/motor cortex [21]. However, cortico-striatal circuits in patients with PD and catatonia can be affected by multiple dysfunctions contributing to changes both in “bottom-up” and “top-down” modulation.

Benzodiazepines and ECT are the mainstay therapy for catatonic symptoms [22]. ECT is highly effective in the treatment of catatonia with response rates ranging from 80% to 100% [23] and is indicated in cases refractory to benzodiazepine treatment or in malignant forms of catatonia. Notably, ECT is also a treatment option for PD patients. According to a systematic review of 116 patients with depression and PD, 93.1% of all patients experienced improvement in depressive symptoms and 83% showed improvement in motor symptoms’ severity. Concurrent improvements in motor symptoms in PD patients treated with ECT for depression may be due to increased dopaminergic neurotransmission [24]. However, the beneficial effect on motor symptoms of PD is probably transient [25]. Despite no conclusions could be made because of few data, no significant deterioration of cognitive functions has been evidenced from baseline to the end of the ECT in these patients. Nevertheless, patients with PD are at higher risk of side effects than those without PD, the most common being delirium and transient confusion [26].

So far, only four cases of catatonia treated with ECT in patients with PD have been described [15–18], three of which showed a significant improvement in psychiatric, motor, and catatonic symptoms after the ECT course. Two additional cases of patients with PD and comorbid bipolar disorder who developed catatonia and were successfully treated with ECT are described in this paper. In both cases, ECT was administered bitemporally using a brief pulse stimulator Mecta 5000Q (Mecta Corporation, Lake Oswego, USA), on a twice-a-week schedule. Parameters included a pulse width of 1.0, duration ranging from 1.5 s to 4.0 s, frequency ranging from 40 Hz to 90 Hz, and a current of 0.8 A. Anesthesia was induced with intravenous thiopental (2–4 mg/kg) and muscle relaxation was assured with succinylcholine (0.5–1 mg/kg). The initial stimulus dosage was based on the “half-age” stimulation strategy for ECT dosing [27]. Motor and electroencephalogram (EEG) seizure duration were monitored. During the ECT course, the stimulus dosage was adjusted to maintain a seizure duration of at least 25 s.

Case report

Discussion

Both of our patients had a diagnosis of bipolar disorder, idiopathic PD, and catatonia. While the first patient had a rather classical course of bipolar disorder type 2, the second one transitioned through several diagnostic categories with increasing severity, experiencing, in order, major depression, hypomania, psychotic depression, mixed mania, and finally, catatonia. In both cases, the diagnosis of PD was clinically established according to the MDS clinical diagnostic criteria for PD by a neurologist with expertise in movement disorders [28]. In fact, both patients had bradykinesia in combination with rigidity and they showed a clear and dramatic beneficial response to dopaminergic therapy. Moreover, their motor symptoms were not better explained by an alternative condition, including iatrogenic parkinsonism. In fact, the patient described in case 1 has never taken antidopaminergic drugs and the patient described in case 2 has taken those medications at a dosage and for a length of time not enough to cause iatrogenic parkinsonism according to the neurologist. This last patient has mostly used quetiapine, one of the antipsychotics with the lowest risk of extrapyramidal side effects [30, 31]. Both patients had a withdrawn type of catatonia with stupor, mutism, and negativism. However, while the former patient first developed depressive symptoms gradually fading into motor inhibition, the second one had a sudden onset of catatonia, possibly emerging from a mixed affective state with both depressive and manic features. Either way, affective symptoms and a history of mood disorders supported the hypothesis that the clinical picture was secondary to a mood alteration rather than to an exacerbation of parkinsonian symptoms. Moreover, both patients did not improve after the anti-Parkinson drugs dose increase, further decreasing the probability of a worsening due to PD. Conversely, both patients improved after ECT. While the patient in case 1 recovered after 8 ECT sessions, 15 ECT sessions were needed before the catatonic signs disappeared in case 2.

Notably, ECT has been found highly effective in patients with bipolar depression and mixed syndromes [32, 33]. Importantly, the severity of psychomotor disturbances, including both motor retardation and agitation, has been positively associated with higher response rates in patients with bipolar disorder or major depression [32, 34]. Despite some authors suggesting the use of unilateral ECT in PD patients in order to reduce cognitive side effects [35, 36], bilateral ECT was adopted in our patients in accordance with most reports of ECT in catatonic patients [37]. Importantly, some authors strongly advocate bilateral ECT in critically ill patients, claiming secondary consideration for transient cognitive impairment in patients with severe catatonia [38, 39]. According to our protocol, however, a less frequent treatment schedule was used to prevent cognitive adverse effects such as delirium. Indeed, bilateral ECT was well tolerated by our patients without worsening cognition or post-ictal delirium.

To the best of our knowledge, only four cases of catatonia treated with ECT in patients with PD have been described [15–18]. Three patients were female and the age ranged between 55 years old and 80 years old. Before the onset of catatonia, all patients had developed psychotic symptoms due to antiparkinsonian medications or attributable to PD progression. Three out of four patients had also had agitation prior to the beginning of catatonia [15–17]. In two cases, the onset of catatonia was closely related to the discontinuation or switch of antiparkinsonian drugs for psychosis [16, 18]. While three patients showed a significant improvement in psychiatric, motor, and catatonic symptoms after the ECT course, residual symptoms of catatonia persisted in an 80 years old woman with recurrent episodes of catatonia and cognitive impairment [17]. The number of sessions ranged from 6 to 12. The electrode positioning was reported only for one patient that had bilateral ECT [15].

Our cases and the four reports discussed above support the role of ECT in the treatment of catatonia in comorbidity with PD. In patients with PD, the diagnosis of catatonia requires a careful neurological assessment because of the symptomatic overlap between the two disorders. Moreover, clinical expertise in the management of catatonia and ECT procedure is needed because of the high risk of side effects in PD patients. Bitemporal positioning with a twice-a-week schedule may have guaranteed good efficacy in our patients, with a low risk of cognitive side effects. Hence, ECT is a valid option for the treatment of catatonia in PD patients. Clinicians who treat catatonic patients with neurodegenerative conditions such as PD should be aware of its safety and efficacy.