CASE REPORT

Pisa-Like Syndrome Under Baclofen in a Patient With Spastic
Hemiparesis due to Ischemic Stroke
Antonino Cannas, MD, Paolo Solla, MD, PhD, Marcello Mascia, MD, PhD, Antonella Muroni, MD, PhD,
Gian Luca Floris, MD, Giuseppe Borghero, MD, Gianni Orofino, MD,
Mario Meloni, MD, and Francesco Marrosu, MD
Abstract: In its original description, Pisa syndrome was reported as an
iatrogenic dystonia of the trunk caused by neuroleptic drugs. However,
sometimes, not dystonic lateral flexion of the trunk is described as Pisa syndrome. These observations support the possibility of a drug-induced lateral
flexion of the trunk with clinical presentation similar to Pisa syndrome, although with a different etiology and pathophysiology. Here, we describe the
case of a male patient, with a previous ischemic stroke and residual spastic
hemiparesis to the right side, who subacutely developed a dramatic lateral flexion of trunk (approximately 45° to the right) a few days after the introduction of
Baclofen (5 mg 3 times per day). After the discontinuation of baclofen, a full
recovery of the correct posture was obtained. In this respect, our case is paradigmatic: it is drug-induced but not clearly dystonic in its manifestation. Baclofen
reduces the spasticity depressing the monosinaptic and polisinaptic reflex in the
spinal cord by stimulating Gamma-aminobutyric acid B (GABA-B) receptors,
which inhibit the release of excitatory amino acids, glutamate and aspartate. We believe that the definition of Pisa syndrome for these forms, not
clearly dystonic, might be not completely appropriate, but they should be
defined more correctly as Pisa-like syndromes.
Key Words: Pisa syndrome, spastic hypertonia, ischemic stroke, baclofen
(Clin Neuropharm 2015;38: 217–219)

T

he term Pisa syndrome is used to indicate a particular postural
deformity characterized by a marked lateral flexion of the
trunk, which is typically mobile and resolves, for example, on lying down.1 The first report on Pisa syndrome was about the onset
of an acute truncal dystonia or pleurothotonus, occurring as a side
effect in 3 elderly women affected by presenile dementia and
treated with antipsychotic treatment.2
Subsequently, descriptions of patients affected by Pisa syndrome have also been reported in patients receiving other drugs,
in those with neurodegenerative diseases, or in idiopathic cases.3–6
More recently, Pisa syndrome has been described in patients
affected by Parkinson disease (PD).7,8
In PD patients, the onset of Pisa syndrome is often subacute,
after a modification of antiparkinsonian therapy, such as the increase in dopaminergic treatment dosage or the introduction of a
Movement Disorders Center, Department of Neurology, Institute of Neurology,
University of Cagliari, Cagliari, Italy.
Address correspondence and reprint requests to Antonino Cannas, Movement
Disorders Center, Department of Neurology, Policlinico, Universitario
Monserrato, SS 554 Bivio per Sestu 09042 Monserrato Cagliari, Italy;
E-mail: antonino.cannas@tiscali.it
A.C. and P.S. contributed equally to the study.
Conflicts of Interest and Source of Funding: The authors have no conflicts of
interest to declare.
P.S. gratefully acknowledges Sardinia Regional Government for the financial
support (P.O.R. Sardegna F.S.E. Operational Programme of the
Autonomous Region of Sardinia, European Social Fund 2007-2013 Axis
IV Human Resources, Objective l.3, Line of Activity l.3.1 “Avviso di
chiamata per il finanziamento di Assegni di Ricerca.”
P.S. has received institutional research funding from the University of Cagliari,
received funding from the Fondazione Banco di Sardegna, and received
research grant from the Dystonia Europe.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/WNF.0000000000000105

novel treatment (ie, dopamine agonists, rasagiline, cholinesterase
inhibitor, Catechol-O-methyl transferase [COMT]).7–13
Although a cholinergic-dopaminergic imbalance in Pisa syndrome was initially supposed, the nature of the lateral truncal flexion is still controversial both regarding pathophysiology and its
suggested dystonic features.1,14 In this scenario, the underlying
pathophysiologic mechanisms probably involved in the development of Pisa syndrome are probably much more complex than
oversimplified models.
In this paper, we present a paradigmatic clinical case
documenting as an iatrogenic lateral flexion of the trunk should
not always be considered as a simple dystonic phenomenon,
because dopaminergic-antidopaminergic drugs are not the only
cause of postural disorders, and suggesting that other pathophysiological mechanisms should be investigated.

CASE REPORT
A 77-year-old male patient recently came for our observation
of a subacute onset of a dramatic lateral truncal flexion of approximately 45° to the right (Fig. 1). This pathological lateral inclination of the trunk appeared a few days after the introduction
of baclofen (5 mg 3 times per day). His medical history revealed
that the patient suffered an ischemic stroke in left middle cerebral
artery territory which resulted in right body spasticity observed
3 years before. With the aim to reduce spasticity, baclofen was
prescribed, although the patient developed a lateral flexion of
the trunk. The neurological examination showed mild weakness
(Medical Research Council Scale for Muscle Strength was 4)
and minimal spastic hypertonia of the right leg, homolateral hypereflexia, and hypotonia of extensor trunk muscles, probably responsible of the lateral flexion. Neurological examination was
negative with regard to any symptom or clinical sign of extrapyramidal disease, and any intake of other known drugs able to induce
lateral flexion of the trunk was excluded. Also, his family history
was negative for movement disorders. For this reason, baclofen
was immediately suspended.
After the discontinuation of baclofen was carried out in about
a week, the full recovery of the correct posture and the subsequent
disappearance of lateral flexion attitude were obtained, proving a
close relationship between drug and adverse effect (Fig. 2).

DISCUSSION
The fact that lateral trunk flexion is not synonymous of Pisa
syndrome is actually an acquired concept. In fact, lateral deviations of the trunk include both Pisa syndrome and scoliosis.14,15
In this regard, whereas several forms of lateral truncal flexion
are clearly associated with osteoarticular disorders, in our patient,
there was a clear drug-related genesis, as in the case of classical
Pisa syndrome.
However, the present case differs substantially from previous
clinical findings, which support the role of an imbalance in basal
ganglia functioning in the pathogenesis of Pisa syndrome. Indeed, according to previous observations, the contribution of

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Clinical Neuropharmacology • Volume 38, Number 5, September/October 2015

Cannas et al

dopaminergic pathways in the pathogenesis of Pisa syndrome is
supported by the description of its occurrence after antidopaminergic drugs exposure,2,3 or in PD patients, by the introduction, increase, or reduction of dopaminergic medications, which
can induce or reverse Pisa syndrome.7–13,16 These findings have
been used to hypothesize that the asymmetry in the basal ganglia
output might contribute to the appearance of the lateral flexion.16
Thus, according this hypothesis, the modification of the dopaminergic treatment might modify the striatal balance and lead
directly to asymmetric regulation of postural muscle tone through
the basal ganglia-brainstem system.14
Notwithstanding the present case, the sudden development
of the lateral trunk flexion does not suggest a primitive asymmetrical imbalance in the basal ganglia output, but could be probably
determined by an acute imbalance of pyramidal muscle tone
(corticospinal pathway) provoked by the introduction of baclofen.
It is useful to remember that spasticity is a very important compensation mechanism which follows the flaccidity of acute injury of cortical-spinal pathway (which represents the maximum
functional disability). After a mild to moderate impairment of
cortical-spinal pathway, the onset of spasticity often helps the recovery of erect posture and walking. In this context of compensation obtained with the increase of spasticity, the acute effect of
baclofen could have modified the equilibrium. In fact, patients
with hemiplegia do not usually develop Pisa syndrome, suggesting that baclofen's action should be considered as the key factor
in its appearance in this patient. With this regard, baclofen reduces the spasticity depressing the monosinaptic and polisinaptic
reflex in the spinal cord by stimulating GABA-B receptors, which
inhibit the release of excitatory amino acids, glutamate, and aspartate. An antispasmodic effect in particular patients and in functionally injured districts can lead to functional damage, leading to
an abnormal flexion posture of the trunk, clinically similar to the
Pisa syndrome, but pathophysiologically different.

FIGURE 2. The same patient after baclofen discontinuation.

Interestingly, previous animal studies indicated that
GABA-B receptors in the substantia nigra pars reticulate, but
not the substantia nigra pars compacta, may play a major role in
the control of nigrostriatal dopamine activity and the release of dopamine in the striatum.17
Nevertheless, baclofen administered orally has a poor ability
to pass the blood-brain barrier, and thus this effect might be likely
in human patients treated by intrathecal administration of baclofen. However, we cannot exclude that Pisa Syndrome could be
partially dystonic in its origin because of the fact that clinical picture and the time course of the phenomenology might be compatible with a form of acute drug-induced dystonia and that the same
baclofen could have played a secondary effect at this level. Unfortunately, a neurophysiological study on trunk muscles, probably
helpful in the identification of electromyographic pattern, was
not performed.
In conclusion, the lateral flexion of the trunk in our patient,
which is only clinically similar to classic Pisa syndrome, supplements the knowledge concerning different physiopathological
genesis of this disorder of posture. For a clearer nosological and
pathophysiological distinction, we believe that these not clearly
dsytonic forms of lateral flexion of the trunk, with entirely different physiopathological bases from classical dystonic Pisa syndrome, might be called “Pisa-like syndrome.”
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FIGURE 1. The patient with Pisa Syndrome during
baclofen administration.

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