Catatonic episode after kidney transplantation☆
Mariusz Kusztal, M.D., Ph.D.a,⁎,1, Patryk Piotrowski, M.D., Ph.D.b,1, Oktawia Mazanowska, M.D., Ph.D.a,
Błażej Misiak, M.D., Ph.D.b,c, Monika Kantorska-Janiec, M.D., Ph.D.b, Maria Boratyńska, M.D., Ph.D.a,
Marian Klinger, M.D., Ph.D.a, Andrzej Kiejna, M.D., Ph.D.b
aDepartment of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland
bDepartment of Psychiatry, Wroclaw Medical University, Poland
cDepartment of Genetics, Wroclaw Medical University, Poland
a b s t r a c ta r t i c l ei n f o
Received 4 November 2013
Revised 30 December 2013
Accepted 7 January 2014
There is a growing body of case reports of catatonic symptoms after organ transplantations. A considerable
number of these cases might be attributed to neurotoxicity induced by immunosuppressive medications.
However, the etiology of other cases remains unclear. We present the case of a 21-year-old woman who
developed catatonia after kidney transplantation from a deceased donor. In this case, nontoxic tacrolimus
levels were found, and other causal factors including infections, uremia or transplant rejection were excluded.
Electroconvulsive therapy followed by olanzapine proved to be effective treatment.
© 2014 Elsevier Inc. All rights reserved.
disturbances that was originally described by Kahlbaum in 1874 .
Until the identification of catatonic symptoms in patients with affective
disorders,catatonia wasexclusivelyregarded asa typeofschizophrenia
. Subsequently, a plethora of case series and single case reports of
catatonia in patients with distinct neurological, psychiatric and
metabolic disorders emerged, indicating that a conceptualization of
catatonia as a syndrome seems to be the most relevant.
2. Case report
A 21-year-old woman, an undergraduate student with end-stage
renal disease, was already 10 months on peritoneal dialysis before
transplantation. She had no psychiatric history except for an episode
of bizarre behavior and consciousness disturbance 11 months before
transplantation that was attributed to uremia toxicity and resolved
during peritoneal dialysis. This episode of delirium was not accom-
panied by catatonic symptoms.
On postoperative day 9, she was discharged from the surgery ward
with satisfactory kidney function, normal tacrolimus level (serum
creatinine: 1.7 mg/dl, tacrolimus level: 8.5 ng/ml) and symptoms of
anxiety and agitation. She received prednisone 15 mg daily,
mycophenolate mofetil 500 mg twice daily and tacrolimus 11 mg
daily. Before transfer to the nephrology ward, she became disorga-
nized, agitated and aggressive toward family members.
On postoperative day 12, she was admitted to the nephrology
ward and referred as afebrile, with normal function of kidney graft
and vital signs with no uremic toxicity. Creatinine level at admission
was 1.1 mg/dl, while the normal range value is under 1.2 mg/dl, and
She refused to eat, drink or take medications.
An extensive medical and neurological workup was essentially
unremarkable except for marginally low magnesium level (1.6 mg/dl)
and white blood cells count of 20.4 × 1000/mL. Her serum tacrolimus
level was normal for the posttransplant period (11.6 ng/ml at
admission, while the target level within first 4 weeks after kidney
transplantation is 10–25 ng/ml). Microbiological cultures including
cerebrospinal fluid and polymerase chain reaction for viruses
(Epstein–Barr virus, herpes simplex virus, parvovirus, cytomegalovi-
rus), C-reactive protein (CRP) and procalcitonin were negative.
Leukocytosis, mainly due to neutrophilia, could result from non-
infectious inflammation and/or prednisone, which was taken in a
higher dose as in early posttransplant period. The inflammatory
diseases like infection were ruled out as CRP, procalcitonin and fluid
cultures were negative. Electroencephalography (EEG) and a head
magnetic resonance imaging were unremarkable.
General Hospital Psychiatry 36 (2014) 360.e3–360.e5
☆ Conflicts of interest: none to declare.
⁎ Corresponding author. Department of Nephrology and Transplantation Medicine,
Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland. Tel.: +48 71 733
2500; fax: +48 71 7332509.
E-mail address: firstname.lastname@example.org (M. Kusztal).
1These authors contributed equally.
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She was conscious without logical contact and with slowed motor
activity. The patient was lying with eyes open and directed straight
ahead. Muscle tone was increased along with exaggerated deep
tendon reflexes in all limbs, which were maintained in a bizarre and
rigid position. Muscle strength was normal, and pathological reflexes
were negative. She made neither verbal nor eye or gesture contact,
offered no spontaneous speech and did not respond to simple
commands. She presented stupor, mutism, staring, posturing, echo-
lalia, echopraxia, rigidity and withdrawal. Severe active and passive
negativism was also present.
Catatonia was diagnosed according to Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition, Text Revision, criteria .
The patient was scored using Bush–Francis Catatonia Rating Scale
(BFCRS) , receiving 46/69 points. The immunosuppressive regimen
was modified — tacrolimus was replaced by cyclosporine iv (an
infusion for 6 h twice daily) and methylprednisolone 40 mg iv, while
mycophenolate mofetil was maintained.
Treatment with diazepam 2.5 mg iv every 6 h was initiated, but the
patient was not improving. Thus, electroconvulsive therapy (ECT) was
patient received 12 points in BFCRS, and only some core psychopath-
ological symptoms were present. She presented inappropriate affect,
distractibility and loss of associations; however, her speech was
temporarily understandable. Apart from correct recognition of family
third-person auditory hallucinations, commentary and abusive voices,
as well as bizarre and persecutory delusions.
She received a course of eight ECT procedures scheduled two per
week, resulting in considerable recovery of catatonic symptoms. The
patient was scored again using BFCRS after the last ECT procedure,
receiving 2 points (postoperative day 51).
In order to augment ECT procedures and target psychotic
symptoms, treatment with olanzapine was initiated. Olanzapine was
started on postoperative day 37 at 2.5 mg orally in the evening to
minimize daytime sedation. The dose was stepwise raised to 10 mg/
day. The patient was discharged on postoperative day 60 with no
catatonic symptoms (0 point in BFCRS) and monitored 1 year long
with no previously described symptoms.
During a control visit at month 6, blood samples were sent for
anti-NMDA receptor, anti-AMPA1 and AMPA2, anti-CASPR2, anti-
GABARB1 and anti-VGKC (anti-LGI1) antibodies. Four weeks later,
anti-LGI1 antibody was reported as positive. Antibodies were
determined using indirect immunofluorescence assay (Autoim-
mune Encephalitis Mosaic, EUROIMMUN, Germany), which is a
Our case displays some resemblance to previously reported cases.
However, to the best of our knowledge, catatonia after kidney-alone
transplantation has not been reported so far. Four cases have been
attributed to neurotoxicity induced by tacrolimus and cyclosporine
[5–8]. Notably, tacrolimus level was within the normal range in our
patient and was replaced by cyclosporine after the development of
catatonic symptoms. Both calcineurin inhibitors may cross the blood
brain barrier and lead to vasogenic edema, but after prolonged
exposure, they may also trigger cytotoxic effects . In other case
reports, catatonia has occurred immediately after organ transplanta-
tion [10,11]. This would suggest that other treatment-independent
mechanisms are involved in the development of catatonic symptoms
after organ transplantation.
In the recent review by Dhossche et al. , some hypotheses
that may correspond with our case were proposed. The authors
provided evidence supporting the role of immune deregulation
in the etiopathogenesis of catatonia. Indeed, catatonia has been
described in a variety of central nervous system infections in the
course of AIDS [13,14], malaria , herpes encephalitis  and
typhoid fever . However, catatonic symptoms often occur in
autoimmune disorders affecting central nervous system including
antiphospholipid syndrome , lupus cerebritis , autoimmune
neuropsychiatric manifestations of streptococcal infection [20,21],
encephalitis lethargica [22–24] and anti-N-methyl-D-aspartate
receptor (anti-NMDAR) encepthalitis [25–28]. Apart from clinical
observations, there is no strong evidence supporting immune and
inflammatory underpinnings of catatonia. As mentioned above,
catatonia might be a clinical manifestation of anti-NMDAR
encephalitis, in which anti-NMDAR antibodies have been found to
reversibly block NMDA receptors, mainly in the hippocampal
regions . In the study by Steiner et al. , acutely ill patients
with an initial schizophrenia diagnosis showed increased preva-
lence of NMDAR antibodies. The repertoire of antibody subtypes in
schizophrenia is different from that with NMDAR encephalitis.
Moreover, the latter disorder should be considered as a differential
diagnosis, particularly in young females with acutely disorganized
behavior or catatonia. Another example of immune alterations is
periodic catatonia, which has been linked to 15q14 chromosome
region . This region contains only four genes (SPRED1, FAM98B,
RASGRP1 and C15orf53). Kranz et al.  found that C15orf53 gene
is expressed within peripheral blood mononuclear cells, as well as
CD4+ and CD14+ immune cells, but not in various brain regions.
The function of this gene remains unclear. In turn, RASGRP1 gene
encodes Ras signaling activator that regulates development,
homeostasis and differentiation of T- and B-cells. Although
catatonic signs in above-mentioned autoimmune disorders have
responded to ECT procedures and benzodiazepines, treatment
strategies targeting aberrant immune response, such as steroids,
plasmapheresis and intravenous immunoglobulin, have been also
proved to be effective .
In our patient, anti-LGI1 IgG positivity was confirmed. In the
literature, tonic seizures in anti-LGI1 encephalitis or epilepsy, but not
catatonia, have been described. LGI1 is a secreted neuronal protein
that functions as a ligand for two epilepsy-related proteins: ADAM22
and ADAM23 . Cardinal symptoms of LGI1 encephalitis are severe
short-term memory impairment with psychiatric symptoms — such
as personality change, depression, anxiety, hallucinations and
confusion — that are accompanied by faciobrachial tonic  and
generalized seizures . Although some LG1 encephalitis symptoms
overlap with those described in our case, seizures that are the cardinal
clinical manifestation were not described, and EEG records were
unremarkable. We hypothesize that anti-LGI1 IgG positivity served as
predisposition to alloimmune response, while surgical trauma and/or
tacrolimus neurotoxicity triggered the onset of catatonic symptoms.
Taking into account a growing body of catatonic episodes in the
course of autoimmune disorders along with evidence for immune
deregulation in our case, it seems that catatonia after organ
transplantation might be the consequence of immune activation or
deregulation. Future studies should focus on investigating immune
alterations in catatonia patients, as direct causal mechanisms of
immune underpinnings have not been investigated so far.
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