Catatonia Secondary to Some Unusual Causes

Sir, Catatonia is a psychomotor syndrome characterized by the presence of three of the following twelve features: stupor; catalepsy; waxy flexibility; mutism; negativism; posturing; mannerisms; stereotypy; agitation; grimacing; echolalia; and echopraxia.[1] It was more readily diagnosed in psychiatry clinics, as it was originally believed to be related to schizophrenia. However, with increase in awareness of catatonia among medical fraternity, catatonia is being recognized in patients suffering from non-psychiatry diseases like neurodegenerative disorders, stroke, encephalitis, head injury, autoimmune disorders and also secondary to drugs like neuroleptics. Due to many overlapping features, catatonia is often confused with extrapyramidal disorders.[2] It is a potentially reversible condition, but a delayed diagnosis may lead to complications like dehydration, deep vein thrombosis, pulmonary embolism, pressure ulcers, and aspiration pneumonia.[3] The list of neurological causes of catatonia is gradually increasing. We, hereby, describe three patients with catatonia secondary to some very unusual causes. A 13-year-old girl presented with new-onset refractory status epilepticus following a bout of flu-like illness. She was diagnosed with N-methyl-D-aspartate (NMDA) encephalitis. Her status epilepticus improved with intravenous immunoglobulins after failing with benzodiazepines, phenytoin, and anesthetic agents. After regaining consciousness, she remained mute. She had intermittent crying spells. In addition, she had spells of restlessness that were characterized by stereotypical truncal and pelvic movements. She had abnormal posturing of limbs and developed marked stiffness of limbs. On examination, she was mute and had rigidity with waxy flexibility, abnormal posturing of limbs with bizarre stereotyped movements of mouth, shoulder, hand, pelvis, and lower limbs. Details of her investigations are given in Table 1. She was treated with gradually escalated doses of lorazepam (10 mg/day) resulting in complete recovery over 2 months.Table 1: Clinical profile of patients of catatoniaA 30-year-old male presented with holocranial headache for 1 year and bilateral progressive painless vision loss for 2 months. On examination, he had only the perception of light. His fundus showed secondary optic atrophy. He had elevated prolactin levels and cranial magnetic resonance imaging (MRI) scan showed a pituitary macroadenoma [Figure 1a]. He was prescribed cabergoline for hyperprolactinemia, which was stopped in the preoperative period. His pituitary macroadenoma was excised. On the second postoperative day, he became mute and rigid and showed facial grimacing. On examination, he had waxy flexibility, gegenhalten, negativism, and intermittent abnormal posturing of limbs. He improved completely with lorazepam and amantadine over the next 4 weeks.Figure 1: (a) Postcontrast T1-weighted axial image showing intensely gadolinium-enhancing solid-cystic sellar mass (black arrow), (b) Postcontrast T1-weighted image showing multiple ring-enhancing lesions with some lesions showing eccentric dot suggestive of a scolexA 23-year-old man presented with reduced interaction with family members progressing to immobility and mutism over 7 days. There was no attempt for self-care. He had a history of seizures for 5 years that were controlled using four antiepileptic medicines (valproic acid, clobazam, levetiracetam, and oxcarbamazepine) for the last 1 year. On examination, he was mute, had intermittent echolalia, gegenhalten, cataplexy, and abnormal upper limb posturing. His cranial MRI showed multiple neurocysticercosis (NCC) in different stages [Figure 1b]. On the first day of treatment with intravenous lorazepam, he started talking. Subsequently, he was kept on oral lorazepam and amantadine. He improved completely in 4 weeks. His antiepileptic drugs were continued. None of the three patients were diagnosed as catatonia by their treating neurologists. The patient with NMDA encephalitis was diagnosed as NMDA encephalitis unresponsive to immunotherapy. Patient with pituitary macroadenoma was diagnosed as having metabolic encephalopathy, and patient with multiple NCC was diagnosed as NCC encephalopathy. Catatonia may mimic other neurological conditions.[2] This might have contributed to the missed diagnoses. The precise pathophysiology of catatonia is unknown. Catatonia is believed to be because of the tonic suspension of motor activity. This is a third defense mechanism in addition to the fight and flight phenomenon.[4] There are three main neuronal circuits critically involved in motor control, movement selection, initiation, timing, and inhibition: a circuit from the primary motor cortex (M1) to the putamen, globus pallidus, thalamus, and back to M1; another includes M1, thalamus, cerebellum, and pontine nuclei; and the final cortico-cortical circuit.[5] This is supported by functional MRI studies that have shown altered activity in various prefrontal areas, thalamus, basal ganglia, amygdala, and other brain areas in patients with catatonia.[5] Therefore, diffuse brain lesions like multiple NCC and NMDA encephalitis (produces diffuse cortical hypometabolism on positron emission tomography studies) may produce catatonia.[6] Psychiatric manifestations like anxiety, depression, and psychosis can occur in patients with disseminated NCC, but catatonia has not been described previously.[7] At the neurotransmitter level, suspension of motor activity or hyper motor activity in catatonia is related to the following: (1) dopamine hypoactivity at the D2 receptor, (2) gamma-Aminobutyric acid (GABA) hypoactivity at the GABA-A receptor and hyperactivity at the GABA-B receptor, (3) serotonin hyperactivity at 5-HT1A receptor and hypoactivity at 5-HT2A receptor, and (4) glutamate hypoactivity at the NMDA receptor.[8] Anti-NMDA antibodies in NMDA encephalitis may produce catatonia because of glutamate hypoactivity at NMDA receptors. Withdrawal of a number of drugs is also well-known to produce withdrawal catatonia. All these agents potentiate GABA in the central nervous system. These drugs include benzodiazepines, alcohol, glutethimide, gabapentin, zolpidem, clozapine, and gamma-hydroxybutyric acid.[9] Clozapine is unique among all the agents that produce withdrawal catatonia because it is both GABAergic and dopamine agonist. The phenotypic characteristics of clozapine withdrawal catatonia are believed to be different from the benzodiazepine withdrawal catatonia because of its complex actions involving neurotransmitters other than GABA—like dopamine and acetylcholine. Cabergoline is also a dopamine agonist drug, and we hypothesize that like clozapine withdrawal, cabergoline’s acute withdrawal led to catatonia in our patient. The cabergoline was not reintroduced in our patient after he developed catatonia because his prolactin levels had normalized by that time, and cabergoline is not a recognized treatment for catatonia despite its dopamine agonist activity. Cabergoline withdrawal catatonia has not been previously described. Irrespective of the etiology, benzodiazepines are accepted as the first-line treatment for catatonia. Benzodiazepines potentiate GABAergic activity in the brain and improve catatonia. Amantadine is a weak NMDA agonist and helps in catatonia by potentiating central nervous system NMDA activity. In schizophrenic catatonia, electroconvulsive activity is sometimes required to overcome catatonia. Electroconvulsive therapy also increases GABAergic activity in the brain. We conclude that catatonia is a potentially reversible psychomotor syndrome. Although rare, catatonia is increasingly recognized in NMDA encephalitis. Cabergoline withdrawal and disseminated NCC can also produce catatonia. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.