neurologia i neurochirurgia polska 50 (2016) 59–62

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Case report

A case report of patient with cerebellar variant of

stiff person syndrome

Ewa Maludzińska a,*, Monika Rudzińska b, Artur Stępień c,

Andrzej Szczudlik d
a
Department of Neurology, The John Paul II Specialist Hospital, Krakow, Poland
b
Department of Neurology, Medical University of Silesia, Faculty of Medicine, Katowice, Poland
c
Nuclear Medicine Department, 5-th Clinical Military Hospital, Krakow, Poland
d
Department of Neurology, University Hospital, Jagiellonian University Medical College, Krakow, Poland

article info abstract

Article history: Stiff person syndrome (SPS) is a rare autoimmune neurological disorder with antibodies
Received 2 July 2014 against antigens involved in neurotransmission of gamma-aminobutyric acid (GABA). About
Accepted 7 November 2015 10% of patients with SPS may develop ataxia. This cerebellar variant is a distinct subset of
Available online 1 December 2015 SPS with more severe and complex clinical phenotype.
We report the clinical, neuropsychological and neuroradiological findings in a 39-year-
Keywords: old female with cerebellar variant of SPS.
Stiff person syndrome Published by Elsevier Sp. z o.o. on behalf of Polish Neurological Society.
Cerebellar ataxia
Cognitive impairment
Glutamic acid decarboxylase
antibodies

limb, although sometimes this progresses to involve the axial

musculature as well. Antibodies against glutamic acid
1. Introduction
decarboxylase (anti-GAD) are diagnostic marker of the SPS,
but they are also described in patients with insulin-depen-
Stiff person syndrome (SPS) is a rare and underdiagnosed dent diabetes mellitus and in patients with cerebellar ataxia.
neurological disorder characterized by the muscle rigidity and Some patients with SPS may develop additional neurologic
superimposed spasms. The rigidity begins insidiously at the abnormalities, including ataxia (10% of patients), epilepsy (5–
truncal muscles and spreads to the legs. Painful spasms are 10% of patients), abnormal eye movements and mental
precipitated by movement, emotional distress and auditory disorders (phobias, anxiety, talkativeness, obsessions).
startle. Some patients do not show the classic axial distribu- Patients with ataxia (the cerebellar variant of SPS) have more
tion of stiffness. It may start focally from one lower limb, severe and complex clinical phenotype of SPS with more
giving rise to the diagnosis of stiff limb syndrome considered prominent stiffness and spasms in the leg and trunk,
as a focal form of SPS in which the symptoms are confined to a cerebellar ataxia; dysarthria; ataxic gait, abnormal eye

* Corresponding author at: Department of Neurology, John Paul II Specialist Hospital, 80 Prądnicka Street, 31-202 Krakow, Poland.
Tel.: +48 126142730; fax: +48 126142729.
E-mail address: neurologia@onet.eu (E. Maludzińska).
http://dx.doi.org/10.1016/j.pjnns.2015.11.003
0028-3843/Published by Elsevier Sp. z o.o. on behalf of Polish Neurological Society.
60 neurologia i neurochirurgia polska 50 (2016) 59–62

movements with impaired saccades, deficient smooth pur-

suit and gaze-holding nystagmus [1,11].
We report the clinical, neuropsychological and neuroradio-
logical findings in a 39-year-old female with cerebellar variant
of SPS.

2. Case report

A 39-year-old woman was referred to the department of

neurology with a three-year history of cerebellar ataxia and
progressive muscle rigidity of axial and limb musculature of
unknown origin. In 2008, she began to complain of unsteady
gait, vertigo and diplopia. Neurological examination revealed
nystagmus and broad-based gait.
Six months later, she reported low back pain and stiffness
in the thoracic and lumbar spine with an exaggerated upright
posture. She developed cramps of thoracic and abdominal
muscles and exaggerated lumbar lordosis. The stiffness has
spread to the proximal limb muscles. The spasms of both legs
and the low back were usually precipitated by passive and
voluntary movement, as well as unexpected noise, but at
times occurred spontaneously. Rigidity increased over
months and patient was virtually unable to walk outdoors
without a cane. Over the last several months, her back spasms
had become progressively more painful with exacerbations
during stressful situations resulting in frequent falls and
difficulty with standing up. She was afraid to walk even with
an aid. Past medical history did not reveal any neurological or
Fig. 1 – MRI of the spine shows an exaggerated lumbar
psychiatric disorder or autoimmune disease. Her family
lordosis.
history was unremarkable. She did not smoke or use illegal
drugs.
On admission, neurological examination revealed sym- Electromyography revealed continuous motor unit activity
metric paraspinal and lower extremities muscle rigidity, an in agonist and antagonist muscles at rest. Magnetic resonance
exaggerated lumbar lordosis and a prominent thoracic scolio- imaging (MRI) of the spine before and after gadolinium
sis with vertical nystagmus, cerebellar dysarthria, mild injection showed thoracic scoliosis and hyperlordosis
dysmetria and dysdiadochokinesia of the upper limbs. A (Fig. 1). MRI of the brain before and after gadolinium injection
slightly increased tone was noted in her left upper limb, but showed no evidence of atrophy of frontal lobes or medial
muscle strength and range of motion were both normal. temporal lobes (Fig. 2).
Strength of the lower limbs could not be assessed because of Single photon emission computed tomography (SPECT)
rigidity and spasms. Sensory examination was normal. Deep studies showed bilateral hypoperfusion in frontal lobes,
tendon reflexes were normal in upper limbs. Knee and ankle especially on the right side (Fig. 3). Visual and auditory evoked
jerks were very brisk bilaterally. Pathological reflexes were potentials were normal. Results of the routine blood biochem-
absent. The gait was slow and stiff because of the rigidity in her ical analyses (including complete blood count, serum electro-
both legs. She had problems to initiate gait and could not walk lytes, blood urea nitrogen, creatinine, glucose, liver enzymes,
unassisted because she was afraid of falling. thyroid-stimulating hormone, ceruloplasmin) and urinalysis
In 2008, neuropsychological study including Rey Auditory were all normal. Anti-GAD autoantibodies were found and
Verbal Learning Test, Clock Drawing Test, Verbal Fluency their level was above 20000 IU/mL (normal value <10 IU/mL).
Test, Trail Making Test, Stroop Test, Wisconsin Card Sorting Anti-amphiphysin and paraneoplastic antibodies were not
Test, serial number subtractions (7 from 100) revealed detected. Gene analysis for spinocerebellar ataxia type 1
impaired selectivity of attention and executive dysfunction. (SCA1) found no abnormalities. Paraneoplastic antibodies
When compared with the neuropsychological assessment were not detected. Analysis of the cerebrospinal fluid (CSF)
completed in 2011 including the same tools, the examination wasn't carried out, because the patient refused lumbar
showed continued impairment of higher-order cognitive puncture.
functions and was suggestive of involvement of frontal- The patient was diagnosed with SPS according to currently
subcortical regions. The assessment revealed increased accepted clinical criteria [1]. Oral diazepam was administered
executive dysfunction and language problems, impairment at the dose of 30 mg daily and marked reduction of the
in short-term memory, learning disturbance, decreased stiffness was observed. The patient was able to walk with a
verbal fluency and mental speed, reduced self-criticism, walking stick. After the increase of diazepam to dose 30 mg/
deficits of attention. day, levetiracetam at 1000 mg/day was introduced. With this
 neurologia i neurochirurgia polska 50 (2016) 59–62 61

Fig. 2 – T2-weighted MRI of the brain.

treatment, her muscle cramps and stiffness diminished and by cerebellar signs or SPS and ataxia may begin concurrently.
her gait improved within a few days. Unfortunately, she had In all patients limb ataxia, dysarthria and visual disturbances
experienced adverse effects (sedation and nausea) and are prominent and are more disabling than axial muscle
levetiracetam was discontinued. Currently, she cannot stand stiffness [1,11,24].
or walk without assistance. At a follow-up visit two months In patients with stiff person syndrome and concomitant
after her initial presentation, she noticed a moderate decrease cerebellar dysfunction increased intrathecal synthesis of anti-
in her stiffness, but loud noises and stressful situations still glutamic acid decarboxylase antibodies (anti-GAD) was found
induced abrupt muscle spasms, primarily involving her lower [1,11]. Intrathecal anti-GAD synthesis is suspected of inducing
back. symptoms in the CNS, presumably by affecting the GABAergic
system. It is suggested that anti-GAD antibodies may also
recognize additional antigenic targets on the inhibitory
3. Discussion
cerebellar interneurons resulting in ataxia [24]. As GABAergic
neurons are critical for brainstem control of eye movements,
Cerebellar variant of SPS results in a combined clinical disruption of GABAergic transmission was proposed as a
symptomatology of SPS and cerebellar disease. Symptoms pathogenic mechanism of oculomotor disturbances in SPS
may start with cerebellar signs followed by muscle spasms and resulting in commonly reported by patients diplopia
stiffness or disease begins with stiffness and spasms followed and blurred vision [3,11,12]. Circulating anti-GAD cause a

Fig. 3 – SPECT showing bilateral hypoperfusion in frontal lobes.

62 neurologia i neurochirurgia polska 50 (2016) 59–62

functional blockade of GABAergic interneurons rather than

Ethics
neuronal loss. On the basis of the pathogenesis drugs
enhancing GABA transmission like sedative-anxiolytics
(diazepam) and antiepileptic drugs (like levetiracetam) has The work described in this article has been carried out in
been recommended in management of spasm and stiffness in accordance with The Code of Ethics of the World Medical
SPS patients [1,8–10]. Association (Declaration of Helsinki) for experiments involv-
A number of associated neuropsychiatric symptoms of SPS ing humans; Uniform Requirements for manuscripts submit-
including anxiety and task-specific phobias have been previ- ted to Biomedical journals.
ously reported in SPS patients, also a slight decline in cognitive
functioning in relation to premorbid levels was suggested [2].
references
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Acknowledgement and financial support cerebellar ataxia and high glutamic acid decarboxylase
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The authors have no relevant financial interest in this article.