Memantine-responsive catatonia secondary to tuberculosis, neurocysticercosis, and pneumococcal pneumonia: A case series

Abstract

Catatonia, a psychomotor disorder, can have underlying psychiatric and medical etiologies. Around 29% of the catatonias with medical etiologies are related to either infectious or immune causes. Benzodiazepines like lorazepam and electroconvulsive therapy are the conventional treatment modalities for catatonia. In this case series, three cases of catatonia secondary to pulmonary tuberculosis, pneumococcal pneumonia, and neurocysticercosis have been described, in which conventional treatment modalities like lorazepam or electroconvulsive therapy either failed or were disadvantageous and were successfully treated with memantine (20–30 mg).

INTRODUCTION

Catatonia is a psychomotor disorder characterized by a set of symptoms like mutism, immobility, negativism, waxy flexibility, etc.[1] It can be a part of a major psychiatric illness like schizophrenia or bipolar disorder or can be secondary to medical conditions, including infections.[1,2] Around 29% of the catatonias secondary to medical causes are related to either infective or immune causes.[1] Catatonia may be life-threatening and needs holistic treatment. Guidelines suggest the use of lorazepam as a first-line agent, and if unsuccessful, electroconvulsive therapy (ECT) should be administered.[3] Glutamate antagonists like memantine have been successfully used in several cases of catatonia in the past.[2,4] Here, we describe three cases of memantine-responsive catatonia secondary to pulmonary tuberculosis, neurocysticercosis, and pneumococcal pneumonia.

CASE SERIES

The clinical information of the patients is detailed in Table 1. All of them were diagnosed with catatonia due to another medical condition according to the Diagnostic and Statistical Manual, 5^th edition (DSM-5),[5] and rated using the Bush Francis Catatonia Rating Scale (BFCRS),[6] both pre- and post-treatment. There was no family history or past history of mental illness, no history of using any psychoactive substance, or any history of chronic medical illness in the past. Facial expression and emotional responsiveness were absent in all patients. No focal neurological deficits were found in any of the patients. Liver function test, renal function test, blood glucose levels, serum electrolytes, thyroid function test, autoimmune panel [anti-neutrophil cytoplasmic, anti-nuclear, anti-thyroid peroxidase, anti- N-methyl-D-aspartate (NMDA) receptor antibodies], magnetic resonance imaging of brain, and cerebrospinal fluid (CSF) analysis in cases 1 and 2 did not reveal any positive findings. The CSF analysis was not done in case 3 due to logistical issues. The patients were initially evaluated by the physicians and admitted under their supervision, and psychiatrist's opinion and treatment were sought through the consultation-liaison service. All the patients failed the lorazepam challenge test (LCT).[3] Cases 1 and 2 were tried further with 6 mg and 8 mg of lorazepam intramuscularly, respectively, but were discontinued due to excessive sedation and the risk of respiratory depression. Case 3 was tried with 10 mg and 14 mg of lorazepam intramuscularly on two successive days following a failed LCT without any significant improvement in BFCRS score. Following a failed lorazepam trial as per guidelines,[3] lorazepam was stopped and memantine immediate release (IR) (20–30 mg) was tried in all the patients. Respiratory comorbidity in cases 1 and 2, the possibility of raised intracranial pressure in case 3, the unwillingness of patients near relatives, and the difficulty of obtaining consent in a catatonic condition limited the application of ECT in these cases. All the patients significantly improved with memantine without any reportable side effects, as evidenced by the change in BFCRS score over the course and reported satisfactory improvement in their psychomotor functioning. Written informed consent was obtained from the patients for this publication.

Table 1.

Details of the included patients

	(Case 1)	(Case 2)	(Case 3)
Patient specific information Presenting medical history	50-year-old married male with primary education, daily wage labourer by occupation 1 month duration of mucoid cough, low-grade fever, fatigue, and dull aching left-sided chest pain, and multiple episodes of hemoptysis with sharp stabbing left-sided chest pain and high-grade fever 2 days before presentation.	48-year-old married female with primary education, housemaker by occupation 5 days of yellowish-colored mucoid cough, high-grade fever with chills and rigor, and right-sided chest pain.	29-year-old unmarried male with primary education, farmer by occupation 2 weeks of a dull, aching headache and a frequent feeling of a reeling sensation in the head.
Catatonic symptoms and BFCRS score	He had immobility, mutism, posturing, negativism, waxy flexibility, withdrawal, and automatic obedience of abrupt onset for around 14 hours. His BFCRS score was 11.	She had immobility, mutism, posturing, rigidity, negativism, waxy flexibility, withdrawal, and automatic obedience of abrupt onset for around 1 day. Her BFCRS score was 13.	He had immobility, mutism, posturing, negativism, waxy flexibility, withdrawal, automatic obedience, and autonomic abnormality of abrupt onset for around 2 to 3 days. His BFCRS score was 14.
Diagnostic assessment and testing	Complete blood count (CBC) showed total leucocyte count (TLC)-14,200/mm3, Haemoglobin-9.8 gm/dl, C-reactive protein-36 mg/L, and ESR- 45 mm/hour, and on 6th day of admission sputum for Acid fast bacilli was reported to be 3+. X-ray chest: Left sided pleural effusion with lower lobe collapse	CBC showed TLC-17,400/mm3, Neutrophil count- 80%, Haemoglobin-10.1 gm/dl, C-reactive protein-34 mg/L, and ESR- 40 mm/hour, and Sputum and Blood culture: Streptococcus pneumoniae. X-Ray chest: Right middle lobe consolidation	CBC – within normal limits. C-reactive protein- 30 mg/L and ESR- 25 mm/h. Non-contrast computed tomography of the brain -multiple round granulomatous lesions with cysts with dot signs were noted, suggesting neurocysticercosis.
Medical treatment	Medical treatment: Ceftriaxone 1 gm intravenous two times a day, Inj Tranexamic acid 500 mg two times a day, and Paracetamol 650 mg sos for fever. Started on anti-tubercular therapy post day 6 of admission [after inpatient care]	Medical treatment: Amoxycillin + Clavulanic 1.2 gm intravenous two times a day and Paracetamol 650 mg sos for fever [after inpatient care]	Medical treatment: Albendazole 400 mg two times and day and Phenytoin 100 mg three times a day orally [started from outpatient visit]
Treatment course with memantine	BFCRS score 6 after 5 days treatment with Memantine IR 10 mg BD, BFCRS score 0 after 10 days treatment with Memantine IR 10 mg TID	BFCRS score 4 after 6 days treatment with Memantine IR 10 mg BD, BFCRS score 0 after 10 days treatment with Memantine IR 10 mg in morning and 15 mg at evening a day	BFCRS score 0 after 7 days treatment with Memantine IR 10 mg BD.
Follow-up and outcomes	Memantine 20 mg is being continued for 1 month till last follow-up along with anti-tubercular therapy	Memantine was tapered by 10 mg every week and stopped and no relapse of catatonia was noted for 2 months till last follow-up	Memantine continued for 1 month till last follow-up.

DISCUSSION

Multiple theories exist regarding the neurobiology of catatonia. The response of the innate immune system to infectious agents, resulting in the rise of inflammatory markers like interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF- α), has been observed in catatonia and catatonia-like phenomena, especially in the context of autoimmune disorders.[1] Experimentally, a decrease in psychomotor activity is slowed as a response to infection, and subtypes of depression like atypical depression and melancholic depression where psychomotor activity is affected are associated with raised pro-inflammatory markers.[1] The NMDA hyperactivity resulting in excess glutamate and glutamate receptor hyperactivity in the parietal lobe has been observed in catatonia.[7] Further, evidence suggests that inflammation in the glial system also activates the NMDA receptors and can result in excess glutaminergic transmission and the accumulation of extracellular glutamate,[8] which can result in catatonia. The catatonic symptoms in our cases may have resulted from these above mechanisms, as there was an underlying infectious cause and a rise in C-reactive protein values.[1] In our cases, catatonia occurred in close proximation with pulmonary tuberculosis, pneumococcal pneumonia, and neurocysticercosis, and given the above-discussed mechanisms and a lack of nullifying evidence regarding the in-between-association, catatonia in our cases was likely secondary to the above infectious etiologies.[9]

Memantine, which acts by blocking NMDA receptors, resulting in reduced abnormal glutaminergic transmission, may reduce catatonia.[2,4] Besides, memantine has also been shown to reduce inflammation-induced oxidative stress, thus reducing neurotoxicity.[10] These mechanisms may be underlying the improvement of catatonia in our cases. The use of conventional benzodiazepines like lorazepam was limited due to the presence of acute respiratory pathologies and sedation, and the use of ECT was also limited. Memantine, having an added beneficial effect on neurocognition, has an advantage over the limitations of conventional modalities for the treatment of catatonia.[2,4]

CONCLUSION

Memantine can be an alternative strategy in patients where conventional treatment modalities for catatonia fail or have disadvantages like the presence of respiratory pathology or raised intracranial pressure. The limitation of this study is that it was observational in nature, without any control group or comparison with conventional treatment.

Declaration of patient consent

The authors declare that they have obtained consent from patients. Patients have given their consent for their images and other clinical information to be reported in the journal. Patients understand that their names 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.