Case Report Treatment of a Prader-Willi Patient with Recurrent Catatonia · form of therapy. ere are no current ECT guidelines for duration of treatment, frequency, strength of treatment,

Case ReportTreatment of a Prader-Willi Patient with Recurrent Catatonia

Hana M. Poser1 and Alexandru E. Trutia2

1Medical College of Virginia, 1201 E. Marshall Street, Richmond, VA 23284, USA2Department of Psychiatry, Virginia Commonwealth University Health Systems, 1300 W. Broad Street, Richmond, VA 23284, USA

Correspondence should be addressed to Hana M. Poser; [email protected]

Received 13 January 2015; Revised 7 April 2015; Accepted 12 April 2015

Academic Editor: Toshiya Inada

Copyright © 2015 H. M. Poser and A. E. Trutia.This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Prader-Willi is a genetic disorder characterized by neonatal hypotonia, hyperphagia, short stature, hypogonadism, and mentaldelay. This disorder can result from multiple mechanisms, most commonly a deletion of paternal chromosome 15, leaving a singlematernally derived chromosome 15. Individuals who have a maternal uniparental disomy of chromosome 15 have a higher risk fordeveloping psychosis compared to other forms of Prader-Willi. The following report details the treatment course of a 24-year-oldfemale with Prader-Willi and recurrent catatonia. The patient initially had a positive lorazepam challenge test but subsequentlyfailed treatment with benzodiazepines. She then received eight electroconvulsive therapy (ECT) treatments after which she showedimprovement from initial catatonic state. However, the resolution in her symptoms did not follow a linear course but would showperiods of improvement followed by a return of catatonic features. This case provides an example of the complexity of treatment ofa patient with a genetic disorder and recurrent catatonia.

1. Introduction

Prader-Willi syndrome (PWS) is a genetic disorder withan incidence of one in 29,000 [1] characterized by absenceof expression of one or more paternally inherited geneson chromosome 15q11-q13. Those with PWS have a char-acteristic phenotype which includes neonatal hypotonia,hypogonadism, short stature, decreased cognition, and mostclassically extreme overeating that can lead to obesity withoutfood restriction. There are four genetic mechanisms whichcan result in the Prader-Willi genotype. Approximately 70%of individuals affected have a de novo deletion of thepaternal chromosome 15 (15q11-q13), 25% of individuals havea maternal uniparental disomy (mUPD) with two copiesof maternal chromosome 15, and the remaining 5% resultfrom an imprinting defect or unbalanced chromosomaltranslocation [2]. Previous studies have shown that thoseindividuals with the mUPD are at a much higher risk forpsychosis than those with PWS due to some other geneticcauses [3, 4]. In addition, individuals with the mUPD had agreater incidence of recurrent psychiatric episodes and oftenthosewith recurrences showed deterioration frompremorbidfunctioning [4]. The limited studies on PWS consist of case

reports and cohort studies with relatively small sample sizesdue to the low prevalence of this syndrome. One case reportexists describing a 17-year-old male with Prader-Willi whopresentedwith catatonia thatwas responsive to pharmacolog-ical therapy alone [5]. The goal of this case report is to detailthe clinical course and treatment of catatonia in a patient withPWS of the mUPD type.

2. Case Report

Ms. Z is a 25-year-old Caucasian female with Prader-WillimUPD type, mild mental retardation (IQ 70), and unspeci-fied mood disorder who presented to the emergency depart-ment after her parents reported one month of increasinglymanic behavior and a ten-pound weight loss in ten days.The patient’s behavior five to six days before hospital admis-sion was described as hyperverbal, euphoric, and illogicalwith decreased sleep. She then suddenly became mute andwithdrawn exhibiting purposelessmovements prompting herparents to bring her to the hospital.

Ms. Z was diagnosed clinically with Prader-Willi at ayoung age with the key features of hyperphagia, short stature,

Hindawi Publishing CorporationCase Reports in PsychiatryVolume 2015, Article ID 697428, 4 pageshttp://dx.doi.org/10.1155/2015/697428

2 Case Reports in Psychiatry

hypogonadism, and mental delay all present. It was not untilthe age of 17 that she underwent genetic testing revealingmUPD form of Prader-Willi. In the past, Ms. Z had twoprior hospitalizations at age of 15 and 16 for depression withcatatonia that responded to therapy with lorazepam andhaloperidol. Before her first hospitalization, Ms. Z had nosignificant psychological history. Since her first hospitaliza-tion, she had been maintained on a variety of antipsychoticand antidepressant regimes for varying diagnosis of mooddisorder not otherwise specified (ICD-10 F39), schizoaffec-tive disorder (ICD-10 F25.9), and depression with psychosis(ICD-10 F33.3) while being followed regularly by a pediatricpsychiatrist. Her current home regimen on presentationconsisted of aripiprazole 25mg daily, lamotrigine 200mgdaily, and lithium 600mg two times a day that the patientwas compliant with. At baseline, Ms. Z is able to work part-time with children under supervision at a local gym and isdescribed by her parents as very friendly and happy. She liveswith her parents who are very involved in her care.

At initial exam, Ms. Z appeared a well-groomed, obeseyoung female with stooped posture and mild hand tremorpresent bilaterally. She appeared drowsy, lethargic, was tearfulat times, and did not make eye contact but was able tofollow simple commands. She displayed mutism, posturing,waxy flexibility, purposeless movements, repeated shouldershrugging, and stereotypy with finger pointing, among otherbehaviors. Bush-Francis Catatonia Rating Scale score totaled21/23. Her affect was blunted and she was orientated toperson but not place or time. Other portions of the examwere not able to be evaluated as patient was unresponsive toquestioning. Physical exam was otherwise unremarkable.

During the interview,Ms. Z responded to 1mg lorazepamchallenge with improved verbal responses although speechwas very slow, soft, and words were slurred. Head CT didnot reveal any acute intracranial abnormality and therewas no evidence of seizure on EEG. She was diagnosedwith catatonia with depressed features and admitted to theinpatient psychiatric unit where she was started on treatmentwith lorazepam 1mg three times a day as well as her homeregimen of antipsychotics.

Over the next 10 days Ms. Z showed minimal improve-ment with lorazepam which was increased to 1mg every 6hours. Her symptoms would fluctuate minimally; at timesshe would be more interactive with staff and family and thenreturn to being withdrawn. During this time, her home regi-men was adjusted by decreasing the aripiprazole and lithiumand initiating therapy with ziprasidone to help with moodand psychosis. Due to lack of response to pharmacologicaltherapy and concern for patient’s well-being with weight lossand dehydration noted on initial presentation, the decisionwasmade to begin ECT therapywith a goal of 6–12 treatmentsdelivered every other day. Ms. Z’s parents were supportive ofthis decision and provided consent for her treatment.

Lithium was discontinued before the start of ECT (referto Table 1 for treatment details) and her morning doseof lorazepam was held on ECT days. After the first ECTtreatment, Ms. Z had improved mental status for about 30minutes and then returned to initial catatonic state. Followingher second treatment with ECT, Ms. Z displayed increased

eye contact, was more verbally responsive, had more energy,described her mood as “happier,” and showed decreasedpsychomotor slowing. During her third ECT session, twostimuli were given due to poor initial motor and EEGseizure responses. The following day, Ms. Z appeared morewithdrawn, appeared less interactive with staff, and againappeared to be responding to internal stimuli. Lamotriginewas decreased and held nights before ECT treatment toachieve better ECT response. Lorazepam was also decreasedto improve motor response to ECT.

After ECT 4, the patient’s progress halted. She displayedincreased psychomotor slowing that was very apparent andMs. Z became very sedated and some of her presentingfeatures of catatonia such as waxy flexibility returned. Shewas spending more time talking to herself and remainedawake for most of the night pacing the hallway. After thisnotable change, lorazepamwas increased due to concern thatthe lower dosage was responsible for a return back towardscatatonic state. Ziprasidone was also increased to help withpsychosis.

The followingmorning,Ms. Z became evenmore sedatedand drowsy, sleeping almost the entire day. Her morninglorazepam was held due to concern over increased sedationand in the following day was again decreased. After ECT5, she was talkative, interactive, and more energetic. Shewas able to participate in group activities and took part indancing, one of her favorite past times. Mini-mental statusexam was performed and the patient received 25/30 onlymissing points for day of the week and date. Her fatherreported at this point that she was “close to baseline.’’

With this improvement, lorazepam was furtherdecreased. ECT 6 was then performed. The night followingECT 6, Ms. Z was noted to be extremely sedated and difficultto arouse.The next morning she providedminimal responsesto questioning, was seen smiling to herself most of the day,displayed unsteady gait, increased psychomotor retardation,and was again very drowsy. She did not have any rigidity orpurposeless movements. It was unclear whether Ms. Z wasmoving back towards her catatonic state or if this was justa normal fluctuation of her catatonic state in response toECT treatment. Lorazepam was discontinued at this time.

ECT 7 was given and over the next three days Ms. Zcontinued to show psychomotor retardation and was mostlymute but began to engage more on the fourth day. LastlyECT 8 was given at 100% bitemporal energy due to decreasedseizure and waxing/waning mutism displayed at the time.Following her final treatment, Ms. Z still displayed somepsychomotor retardation and decreased energy but did havespontaneous speech. Her parents felt she was about 70% ofher baseline.The following day, she was able to be dischargedhome after 29 days of inpatient treatment. She was dischargedon lamotrigine 150mgdaily, lithium300mg three times a day,and ziprasidone 120mg daily. At her tenth week of follow-up,Ms. Z’s mood had improved. She was able to return to workalthough she was experiencing some episodes of cataplexy.

Case Reports in Psychiatry 3

Table1:EC

Ttre

atmentcou

rse.

ECT

Medications

Energy/charge

Motor/EEG

respon

seClinicalrespon

se

1Ziprasidon

e60m

gtwiced

aily,

lamotrig

ine2

00mg

before

bed,andlorazepam

1mgthreetim

esdaily

25%bifro

ntal

128.9m

c1sec

motor/36s

ecEE

G

Improved

verbalrespon

sefor3

0min

andthen

back

tocatatonics

tate.Th

roug

hout

thed

ay,patient

becamem

orev

erbaland

coherent

andeven

expressedhu

mor.

2Identic

alregimen

astim

epoint

140

%bifro

ntal

204.2m

c10secm

otor/40s

ecEE

GLessinteractive,disorie

nted,w

ithrepetitive

movem

ents.

3Identic

alregimen

astim

epoint

150%/75%

bifro

ntal

1

258.7m

c

1sec

motor/7secE

EG5sec

motor/48s

ecEE

GLessenergetic

,increasinglydrow

sy,m

inim

alinteraction,

decreasedsle

ep,and

pacing

hallw

ays.

4Ziprasidon

e60m

gtwiced

aily,

lamotrig

ine150

mgbefore

bed,andlorazepam

0.5m

gthreetim

esdaily

75%bifro

ntal

377.4

mc

33secm

otor/56s

ecEE

GVe

rydrow

sy,psychom

otor

retardation,

decreased

sleep,w

axyflexibility,andincreasedspeech

latency.

5Ziprasidon

e80m

gtwiced

aily,

lamotrig

ine150

mgbefore

bed,andlorazepam

0.5m

gthreetim

esdaily

75%bifro

ntal

376.1m

c21secm

otor/29s

ecEE

GMuchmoree

ngaged,aware,conversatio

nal,and

oriented

tosituatio

n.

6Ziprasidon

e80m

gtwicea

day,

lamotrig

ine150

mgbefore

bed(held

before

ECT),

andlorazepam

0.5twiced

aily

100%

bifro

ntal

502.4m

c19secm

otor/34s

ecEE

GWaxing/waningmutism

,repetitive

movem

ents,

and

psycho

motor

retardation.

7Ziprasidon

e80m

gtwiced

aily,

lamotrig

ine150

mgbefore

bed(held

before

ECT),

andd/clorazepam

100%

bifro

ntal

503.2m

c19secm

otor/34s

ecEE

GIm

proved

butstillw

ithlowenergy

andvery

drow

sy.

8Ziprasidon

e40m

gam

/80m

gpm

,lam

otrig

ine

150m

gbefore

bed

100%

bitempo

ral

502.9m

c11secm

otor/56s

ecEE

GRe

gainingenergy,m

oree

ngaged,w

ithim

proved

affect.

Morning

dose

oflorazepam

was

held

inmorning

sofE

CTforb

etterseizure

respon

se.

1 Treatmentrequiredtwostimulid

ueto

poor

motor

respon

se.

4 Case Reports in Psychiatry

Sixmonths after hospitalization, she hadmade a full recoverywith no return of catatonic features.

3. Discussion

Catatonia is a recognized syndrome characterized by itsunique set of behavioral abnormalities and response tobenzodiazepines and ECT. Multiple models have been pro-posed to explain the etiology of these behaviors includingtheories on dysfunctional GABA receptors and alterationsto hypothalamic-pituitary axis [6]. Some also suspect thatthere could be a genetic component to the developmentof catatonia. Catatonia can be one of the displayed formsof psychosis seen in individuals with Prader-Willi which iscaused by an abnormality in chromosome 15. Similar geneshave been implicated in catatonic schizophrenia and autism[6].

Due to the lack of randomized controlled trials address-ing the treatment of catatonia, protocol for therapy is mainlybased on case reports and retrospective studies. Currently,benzodiazepines followed by ECT or simultaneous use ofboth represents the standard of care. Case series suggest thatbenzodiazepines alone have a response rate of 60%–80% [7].For patients with severe catatonia or catatonia refractory totreatment with benzodiazepines, ECT is the recommendedform of therapy. There are no current ECT guidelines forduration of treatment, frequency, strength of treatment, orelectrode placement in patients with catatonia due to lack ofcontrolled studies using ECT in this target population. Onerecent study of 63 patients treated with ECT for catatoniafound the average number of ECT sessions per patient tobe 7.25 ± 2.54 with an 88.89% response rate [8]. Varia-tions in electrical charge delivered and duration of motorand EEG response can been seen between retrospectivestudies.

As seen in this case, the treatment course becomescomplex when dealing with catatonic patients with comorbidgenetic and mood disorders being treated with mood stabi-lizers and antipsychotics. It becomes difficult to discern whataspects of treatment are contributing to improvement andthose that may be hindering it. In addition, the response toECT can be highly variable among patients and symptomscan seem to fluctuate throughout the course of treatmentas seen with Ms. Z. The study by Raveendranathan et al.suggests that characteristics such as younger age, durationof catatonia, and higher Bush Francis may predict bet-ter response to ECT. One consistent finding among stud-ies was that earlier diagnosis and treatment of catatonialed to better outcomes. This stresses the importance ofearly recognition of symptoms, diagnosis, and treatment ofcatatonia.

A database search locates one other case report of catato-nia in a patient with Prader-Willi. This case study describedthe treatment of a 17-year-old male with Prader-Willi, whowas diagnosed clinically and had acute onset catatonia whichresponded to treatment with lorazepam and risperidone overa two-week period [5]. Ms. Z who was described here with

Prader-Willi of the maternal uniparental disomy type wasknown to have a preexisting mood disorder and receivedtreatment for recurrent catatonia refractory to treatment withbenzodiazepines.

Consent

Verbal consent for publication was given by patient’s mother.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

References

[1] J. E.Whittington, A. J.Holland, T.Webb, J. Butler, D. Clarke, andH. Boer, “Population prevalence and estimated birth incidenceandmortality rate for peoplewith Prader-Willi syndrome in oneUK Health Region,” Journal of Medical Genetics, vol. 38, no. 11,pp. 792–798, 2001.

[2] R. D. Nicholls and J. L. Knepper, “Genome organization,function, and imprinting in Prader-Willi and Angelman syn-dromes,” Annual Review of Genomics and Human Genetics, vol.2, pp. 153–175, 2001.

[3] H. Boer, A. Holland, J. Whittington, J. Butler, T. Webb, and D.Clarke, “Psychotic illness in people with PraderWilli syndromedue to chromosome 15 maternal uniparental disomy,” TheLancet, vol. 359, no. 9301, pp. 135–136, 2002.

[4] S. Soni, J. Whittington, A. J. Holland et al., “The courseand outcome of psychiatric illness in people with Prader-Willi syndrome: implications for management and treatment,”Journal of Intellectual Disability Research, vol. 51, no. 1, pp. 32–42, 2007.

[5] D.M.Dhossche andN.H. Bouman, “Catatonia in an adolescentwith Prader-Willi Syndrome,” Annals of Clinical Psychiatry, vol.9, no. 4, pp. 247–253, 1997.

[6] D. M. Dhossche, L. Stoppelbein, and U. K. Rout, “Etiopatho-genesis of catatonia: generalizations and working hypotheses,”Journal of ECT, vol. 26, no. 4, pp. 253–258, 2010.

[7] A. Francis, “Catatonia: diagnosis, classification, and treatment,”Current Psychiatry Reports, vol. 12, no. 3, pp. 180–185, 2010.

[8] D. Raveendranathan, J. C. Narayanaswamy, and S. V. Reddi,“Response rate of catatonia to electroconvulsive therapy and itsclinical correlates,” European Archives of Psychiatry and ClinicalNeuroscience, vol. 262, no. 5, pp. 425–430, 2012.

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Case Report Treatment of a Prader-Willi Patient with Recurrent Catatonia · form of therapy. ere are no current ECT guidelines for duration of treatment, frequency, strength of treatment,