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Indian J Psychiatry
Indian J Psychiatry
IJPsy
Indian J Psychiatry
Indian Journal of Psychiatry
0019-5545
1998-3794
Wolters Kluwer - Medknow India

IJPsy-66-675
10.4103/indianjpsychiatry.indianjpsychiatry_322_24
Letters to Editor
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) presenting as catatonia: A case report in a psychiatry setting
Sahoo Swapnajeet
Chaurasia Nishtha
Yadav Nidhi
Kapila Aastha T. 1
Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India E-mail: swapnajit.same@gmail.com
1 Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
7 2024
17 7 2024
66 7 675678
13 4 2024
17 6 2024
18 6 2024
Copyright: © 2024 Indian Journal of Psychiatry
2024
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pmcINTRODUCTION

Catatonia has always been in the limelight of psychiatric nosological systems and now has been assigned a special chapter in DSM-5.[1] Catatonia secondary to general medical condition, more commonly called as organic catatonia, is being increasingly recognised in the recent years.[2] Few studies have also described the symptom profile, etiological aspects, and treatment response of organic catatonia.[34]

FENIB is a rare hereditary degenerative condition of the central nervous system.[5] Individuals with this condition exhibit low attention and focus, diminishing work or academic performance, and language difficulties and eventually endure a deterioration in intellectual capacities (dementia).[6] There have reports of additional symptoms, such as uncontrollable, erratic muscular spasms, seizures, mood changes including apathy, despair, and hostility.[78] Eventually, the afflicted individuals need thorough supportive conservative medical care and management of comorbid conditions (myoclonus, seizures etc.). The key pathological finding in FENIB is the presence of neuronal inclusion bodies distributed throughout the gray matter of the cerebral cortex and in certain subcortical nuclei.[5] However, FENIB presenting as catatonia is not yet reported, and probably ours is the first case report in this regard, suggesting to include FENIB in the list of etiological conditions of organic catatonia.

CASE DESCRIPTION

The index patient was a 24-year young female, studied till 9th standard, from a nuclear family, of lower middle socioeconomic status, second in birth order, born out of full-term normal vaginal delivery, maintained well during childhood, and attained all the developmental milestones normally for her age with poor scholastic performance. As per the informants (parents), she was able to do all household chores, was able to understand the concept of money, and reportedly was fast in grasping all the concepts. She failed in her 10th standard, and thereafter, she did not wish to study further. She used to help with all the household chores efficiently until around 2016, would interact with family members, and would be euthymic. In 2016, when she was around 17 years of age, with apparently no precipitating event, she started to avoid doing household chores, had reduced interaction with family members, had decreased emotional reaction on hearing any sad or happy news, and would not actively participate in any family discussion which was quite unlike her premorbid self. She would be seen sitting idle in front of the television for the whole day in the same place. She would keep looking in one direction for a period of 2 to 3 minutes without blinking. She would not bathe, brush, and eat by herself; would eat only when served; and did not show much change in facial expressions. On many occasions, she noted to wear her clothes upside down and would not bother much about the same; during her menstrual cycle, the patient would not take care of her hygiene.

Over the years, she gradually started to respond in very few sentences or just by nodding her head in yes or no. Due to gradual worsening of her condition, she was brought to our outpatient psychiatric services in October 2023 and a diagnosis of Catatonia was considered with possibility of an underlying psychotic illness (schizophrenia with predominantly negative symptoms). When rated on Busch Francis Catatonia Rating Scale (BFCRS), she scored 14, but on administering 2 mg intravenous lorazepam (Lorazepam Challenge Test), it was negative (no change in BFCRS score). A working diagnosis of catatonia and simple schizophrenia was kept, after which she was planned for electroconvulsive therapy (ECT). She was started on Tab. Aripiprazole 5 mg OD. However, in the next few days, her catatonic signs and symptoms worsened (posturing, staring, negativism, closing her mouth on being fed, resisting any possible body movement, and even started to pass urine and faces in her clothes). Ten effective modified ECTs were administered, and she was admitted to our inpatient psychiatric services for diagnostic clarification. Following ECTs, she had gradual reduction in the catatonic signs, and BFCRS score reduced to 4 [Table 1].

Table 1: Rating on the Bush Francis Catatonia Rating Scale on serial evaluation and response to ECT

Items on BFCRS	9.10.23 Baseline score	17.10.23 Score after 1st ECT)	23.10.23 Score after 4th ECT)	30.10.23 Score after 7th ECT	15.11.2023 Relapse of catatonic symptoms after 2 weeks of stopping ECT	Score after restarting of ECT (after 7 consecutive ECTs – 3 ECTs/week)	Score at follow-up ECT – after one month	
Immobility/stupor	2	2	2	1	2	1	0	
Mutism	3	3	2	1	3	1	0	
Staring	2	3	2	1	2	1	0	
Posturing/catalepsy	2	1	1	0	2	0	0	
Grimacing	0	0	0	0	0	0	0	
Echopraxia/echolalia	2	1	1	0	1	0	0	
Stereotypy	0	0	0	0	0	0	0	
Mannerisms	0	0	0	0	0	0	0	
Stereotyped & meaningless repetition of words & phrases (verbigeration)	1	0	0	0	0	0	0	
Rigidity	2	1	0	1	2	0	0	
Negativism	2	2	0	0	2	0	0	
Waxy flexibility	0	0	0	0	0	0	0	
Withdrawal	0	0	0	0	0	0	0	
Excitement	0	0	0	0	0	0	0	
Impulsivity	0	0	0	0	0	0	0	
Automatic obedience	2	0	0	0	0	0	0	
Passive Obedience (mitgehen)	2	0	0	0	0	0	0	
Muscle Resistance (gegenhalten)	3	0	0	0	0	0	0	
Motorically Stuck (ambitendency)	3	0	0	0	2	0	0	
Grasp reflex	0	3	0	0	0	0	0	
Perseveration	3	0	0	0	0	0	0	
Combativeness	0	0	0	0	0	0	0	
Autonomic abnormality	0	1	0	0	1	0	0	
Total BFCRS Score	29	17	12	4	17	3	0	

In ward observation and serial mental state examination, she was found to behaving oddly, would be seen smiling inappropriately, would not understand any commands, and continued to pass urine and stool in her clothes and appear unbothered by it. She was found to have severe inattention, echolalia and echopraxia (repetition of same words and actions), perseveration (continuous type abnormally prolongs or repeats a behaviour without interruption), utilization behaviour (she tried holding any object handed near to her), grasp reflex present, and frontal release signs. In neurological examination, she had brisk deep tendon reflexes (3+), and plantar reflex was flexor. Rigidity was present in all the four limbs (4/5); however, it could be due to catatonic negativism. Fundus examination was normal. Tab aripiprazole 5 mg was stopped in the first week, and after 2 weeks of stopping ECTs, she had relapse of catatonia with BFCRS score rising up to 17. ECTs were restarted, and after 7 ECTs, catatonia improved [Table 1]. Neurology consultation was taken in view of suspicion of organicity as there was the presence of diffuse cerebral atrophy on MRI (brain) at the young age of 24 years. All the metabolic parameters including serum ceruloplasmin and blood levels for heavy metals were normal. Following which blood investigation for whole genome exome sequencing was sent (report usually takes 1 month time). She was kept on weekly maintenance ECTs as every time a gap of 5 days of ECT was given, she had relapse of catatonic signs and she was discharged from inpatient psychiatric facilities. Around 1 month later, she developed an episode of generalized tonic clonic seizures (lasting for 2 to 3 minutes) and was unconscious for 20 to 25 minutes. Electroencephalogram (EEG) revealed seizure activity, and she was started on phenytoin 300 mg/day. The whole genome exome report revealed that she had a heterozygous variant of uncertain significance in exon 9, SERPINI1 gene (variant – c.1178G.C, p. Arg393Pro, Depth-64x; Genomin nomenclature – Chr 3;g.167543056G>C), which had an autosomal dominant inheritance and was diagnosed with familial encephalopathy, with neuroserpin inclusion bodies. Family members were counselled about the diagnosis and future expectations from treatment. Genetic testing of parents could not be done due to financial constraints. There was no family history of epilepsy of similar symptoms in parents or in any relatives. The absence of similar symptoms in parents could possibly be due to de novo mutation resulting in a pathogenic variant, as has been reported in a few case reports.[9] Due to frequent relapse of catatonia, she had been kept on maintenance ECTs every fortnightly and phenytoin 300 mg/day from neurology. On follow-up until date, she is maintaining reasonably well and able to do self-care activities but is having gradual cognitive decline as evident from assessment of Hindi Mini-Mental State Examination Scale ranging from 15 to 17 always (which is the natural course of the disease – FENIB).

DISCUSSION

The index case highlights the importance of evaluating for organic cause in patients presenting with catatonia with unusual presentation. The patient initially presented with symptoms suggestive of negative symptoms of schizophrenia and subsequently presented with catatonia, which almost simulated the presentation of catatonic schizophrenia.[10] However, after a thorough investigation and the hunch of the possibility of organic cause (due to frequent relapse of catatonia when ECTs were stopped/spaced in the absence of any gross psychotic/positive symptoms along with cognitive impairment at a young age), we were able to reach to the diagnosis of FENIB. In many secondary and tertiary care psychiatric settings in low and middle-income countries, the facilities to perform a thorough organic workup are not available, and hence, many a time, many patients with unusual presentation with catatonia are labelled/misdiagnosed as schizophrenia/psychosis, and are treated with multiple antipsychotics/other types of treatment strategies.[111213]

The age of onset, rate of progression, and severity of FENIB varies depending on the specific mutation in the neuroserpin gene.[5] The symptoms of FENIB may become apparent as early as the first decade or as late as the fifth or sixth decade of life. Our knowledge of FENIB is limited by the fact that only a few families with FENIB have been described.[61415]

In late onset illness, affected individuals typically experience declining cognitive function that affects their ability to work. In addition to deficits in attention, concentration, and language usage, an impaired ability to judge the spatial relationship between objects (poor visuospatial skills). A striking finding is perseveration, a condition marked by uncontrolled, repetitive behaviors such as continually repeating a word, phrase, or gesture, present in the index case.[5] Daily living skills are gradually lost, and they become increasingly dependent on family or other care givers. Eventually, most will require comprehensive care in a skilled nursing facility. Other symptoms may include tremor, motor restlessness, dystonia (sustained muscle contractions associated with abnormal, uncontrolled movements and postures), and occasionally seizures.[8] The rate of decline is relatively slow, and with adequate supportive care, patients may survive for many years or even decades.[5]

When FENIB begins earlier in life, from the first to third decade, there are additional neurological symptoms and the disease may progress quite rapidly. Seizures may be the first manifestation, including a syndrome called progressive myoclonic epilepsy (PME).[78] The seizures may be difficult to control with medication, and episodes of status epilepticus or persistent, repetitive seizures may occur, sometimes resulting in death. In general, an earlier age of onset is associated with more severe symptoms, and the patient may survive for only a few years.[16] Cognitive deficits have been mostly reported in frontal and frontal-subcortical areas in the reported cases across the globe.[6]

Few case reports suggest that patients with G392R and G392E variants have onset of symptoms at the age of 7–8 yrs and 11–13 years, respectively (i.e., childhood onset FENIB) and often present with PME and gradual cognitive decline.[9] In the index case, the onset of symptoms started around the age of 17 years and had G393 variant in exon 9 of chromosome 3.

The treatment of FENIB is directed toward the specific symptoms that are apparent in each individual. Individuals with progressive dementia often experience frustration, anxiety, and depression due to their decreasing ability to function in certain aspects of their lives.[5] These frustrations may be minimized by maintaining a stable home environment and a structured routine that does not place excessive demands on the affected individual. Eventually, most individuals with FENIB require comprehensive medical care as provided in a nursing home. Genetic counselling is recommended for affected individuals and their families.[5]

Catatonia as presenting symptom in a case of FENIB has not been reported yet, and therefore, ours is the first case to report this finding, which resolved with ECT, further highlighting the role of ECT in the management of organic catatonia not responding to lorazepam. As evident from the recent literature review, FENIB is limited to a handful of case reports, suggesting the need for more research on this disorder.[9] A close collaboration between psychiatrists, neurologists, and physicians is needed to diagnose and manage patients with FENIB.

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.

Acknowledgements

We acknowledge the patient and her parents for allowing us to publish this case study.
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REFERENCES

1. Tandon R Heckers S Bustillo J Barch DM Gaebel W Gur RE Catatonia in DSM-5 Schizophr Res 2013 150 26 30 23806583
2. Fink M Catatonia from its creation to DSM-V: Considerations for ICD Indian J Psychiatry 2011 53 214 7 22135438
3. Bhuvana PV Abhiram PN Vaidyanathan S Praharaj SK Clinical profile of Organic Catatonia- A case series Indian J Psychiatry 2022 64 Suppl 3 S557
4. Grover S Sahoo S Chakravarty R Chakrabarti S Avasthi A Comparative study of symptom profile of catatonia in patients with psychotic disorders, affective disorders and organic disorders Asian J Psychiatry 2019 43 170 6
5. Davis RL Holohan PD Shrimpton AE Tatum AH Daucher J Collins GH Familial encephalopathy with neuroserpin inclusion bodies Am J Pathol 1999 155 1901 13 10595921
6. Bradshaw CB Davis RL Shrimpton AE Holohan PD Rea CB Fieglin D Cognitive deficits associated with a recently reported familial neurodegenerative disease: Familial encephalopathy with neuroserpin inclusion bodies Arch Neurol 2001 58 1429 34 11559315
7. Ranza E Garcia-Tarodo S Varvagiannis K Guipponi M Lobrinus JA Bottani A SERPINI1 pathogenic variants: An emerging cause of childhood-onset progressive myoclonic epilepsy Am J Med Genet A 2017 173 2456 60 28631894
8. Roussel BD Lomas DA Crowther DC Progressive myoclonus epilepsy associated with neuroserpin inclusion bodies (neuroserpinosis) Epileptic Disord 2016 18 S2 103 10 27618835
9. Yang X Fang Z Yan L He X Luo H Han Z Role of SERPINI1 pathogenic variants in familial encephalopathy with neuroserpin inclusion bodies: A case report and literature review Seizure 2022 103 137 47 36417830
10. Jain A Mitra P Catatonic Schizophrenia StatPearls Treasure Island (FL) StatPearls Publishing 2024
11. Fu R Chen Y Cao S Case of catatonia misdiagnosed with coma Gen Psychiatr 2020 33 e100059 32090193
12. Gama Marques J Twenty years of misdiagnosis of schizophrenia in a patient with Dandy-Walker variant syndrome Gen Psychiatr 2019 32 e100031 30815635
13. Giamarelou A Polychronopoulos P Skokou M Messinis L Gourzis P Frontotemporal dementia misdiagnosed as schizophrenia or other psychotic disorder Eur Psychiatry 2017 41 S812
14. Amano-Takeshige H Oyama G Kanai K Miyagawa T Mitsui J Ugawa Y A Japanese family with mutation in the proteinase inhibitor 12 L47P gene: A case report J Neurol Sci 2018 384 126 8 29249370
15. Chen S He S Pang M Li W Li S Zhang J A Chinese pedigree of familial encephalopathy with neuroserpin inclusions bodies Chin J Neurol 2021 12 649 54
16. Hagen MC Murrell JR Delisle MB Andermann E Andermann F Guiot MC Encephalopathy with neuroserpin inclusion bodies presenting as progressive myoclonus epilepsy and associated with a novel mutation in the Proteinase Inhibitor 12 gene Brain Pathol 2011 21 575 82 21435071
