CASE REPORT
(Pseudo)hemidystonia associated with anti-glutamic acid decarboxylase antibodies – a case report J. Kendaa, M. Kojovic´a, F. Grausb and M. Gregoric Krambergera a
Department of Neurology, University Medical, Center Ljubljana, Ljubljana, Slovenia and bDepartment de Neurologia, Hospital Clı´nic, Barcelona, Spain Correspondence: M. Gregoric Kramberger, Department of Neurology, University Medical Center Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia (tel.: +38615222311; fax: +38615223037; e-mail: [email protected]).
Keywords: anti-GAD antibodies, dystonia, pseudodystonia, stiff person syndrome
a supine position and could perform a few steps with a walker (Video S1). Brain magnetic resonance imaging (MRI) was normal, with no structural lesions in basal ganglia or thalamus. Spinal MRI showed lateral disc herniation at the C6–C7 level with left C7 root compression, presumably resulting from prolonged and fixed neck posture. Baseline cerebrospinal fluid (CSF) analysis was normal, oligoclonal bands were negative. Complete blood count, renal and hepatic function tests, thyroid hormones were normal. Anti-TPO antibodies were highly raised (>1300 kU/l), consistent with the known diagnosis of chronic lymphocytic thyroiditis. Fludeoxyglucose positron emission tomography showed normal metabolism in basal ganglia bilaterally. Anti-neuronal antibodies (anti-Hu, Yo, Ri, CV2, amphiphysin, Ma1, 2) and
neuronal surface antibodies (NMDA, AMPA1, AMPA 2, GABA, LGI1, CASPR2 and GlyR) were negative in serum and CSF. However, a high titer of autoantibodies against glutamic acid decarboxylase (GAD) was detected in both CSF (1:80) and serum (1:10 000). The specific anti-GAD intrathecal index (adjusted to total immunoglobulin G) was 3.3, a value compatible with intrathecal synthesis. Electromyography showed continuous motor unit activity at rest in gastrocnemius and tibialis anterior muscle, paraspinal and neck muscles. She was diagnosed with stiff person syndrome (SPS). Treatment consisted of diazepam (up to 60 mg/day), baclofen (25 mg/day) and intravenous immunoglobulins (0.4 g/kg for 5 days) at 4–6 week intervals. Clinical improvement was noticed: she was able
doi:10.1111/ene.12700 Received: 16 November 2014 Accepted: 6 February 2015 A 55-year-old woman with a history of diabetes mellitus type 1, chronic lymphocytic thyroiditis, vitiligo and no history of head or spine injury presented in May 2013 with abnormal painful posturing of the left hemibody. At the beginning of 2012 she noticed pain between the shoulder blades further progressing to affect the neck. By the end of 2012 her head was tilted to the left, shoulder was elevated and she was unable to straighten her neck. In January 2013 the pain appeared also in her left ankle, which gradually became immobile. On admission she had isolated left hemibody signs with fixed dystonic posture of the neck with left lateral flexion, left shoulder elevation, trunk deviation to the left, fixed left knee and foot plantar flexion (Fig. 1). There was no fluctuation in abnormal body posturing, no sensitivity to external stimuli and no sensory trick. She had no cognitive, psychiatric or cerebellar features to suggest Hashimoto encephalopathy, a disease in which cooccurrence of lymphocytic thyroiditis and dystonia has been described [1]. She needed assistance with standing up from
© 2015 EAN
(b) Fixed dystonic posture of the neck with left lateral flexion and shoulder elevation.
(a) Trunk deviation to the left.
(c) Fixed left knee flexion and foot plantar flexion. Figure 1 Clinical features. (a) Trunk deviation to the left. (b) Fixed dystonic posture of the neck with left lateral flexion and shoulder elevation. (c) Fixed left knee flexion and foot plantar flexion.
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CASE REPORT
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to move the neck in all directions for 20°–30°, fully extend the knee and make 30° of foot dorsiflexion. However, prolonged (up to 8 week) intervals between infusions resulted in worsening of gait and falls, which eventually resulted in a right hip fracture, followed by intensive rehabilitation. Classical clinical phenotype of antiGAD antibody-positive patients with SPS includes axial stiffness with superimposed episodic spasms and stiff gait. When stiffness is prominent in one leg, it is referred to as the stiff leg syndrome [2]. Our patient is unusual as she presented with abnormal fixed postures in the strict hemi-distribution, first involving neck with left lateral flexion, then trunk and left leg. When facing a patient with hemidystonia, contralateral basal ganglia or thalamic structural lesion should be thought of first [3]. This was excluded in our case. Other considerations, particularly in the presence of painful fixed dystonic posturing, are psychogenic dystonia and pseudodystonia [4,5]. Pseudodystonia refers to abnormal postures of body parts that are not caused by disorders of basal ganglia, e.g. fixed neck postures due to
cranio-vertebral junction disorders, limb contractures complicating spasticity and last but not least SPS [5]. In our patient, the history of diabetes type 1, thyroid disease and vitiligo suggested that she was predisposed to autoimmune disease [6] and thus prompted us to consider SPS and testing for anti-GAD antibodies. Some patients with fixed dystonic postures of the limb(s) or hemi-body (and in the absence of structural brain lesion) may be misdiagnosed as psychogenic if SPS is not considered in the differential diagnosis, particularly when associated with other autoimmune disorders. This is important to recognize because SPS is potentially treatable with immunosuppressive therapy. Disclosure of conflicts of interest The authors declare no financial or other conflicts of interest.
Supporting Information
Video S1. Vitiligo around the eyes is evident. References 1. Tang Y, Chu C, Lin MT, et al. Hashimoto’s encephalopathy mimicking spinocerebellar ataxia. J Neurol 2011; 258: 1705–1707. 2. Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology 2000; 55: 1531–1535. 3. Marsden CD, Obeso J, Zarranz J, Lang A. The anatomical basis of symptomatic hemidystonia. Brain 1985; 108: 463–483. 4. Ganos C, Edwards MJ, Bhatia KP. The phenomenology of functional (psychogenic) dystonia. Mov Disord Clin Pract 2014; 1: 36–44. 5. Jankovic J, Fahn S. Dystonic disorders. In: Jankovic J, Tolosa E, eds. Parkinson’s Disease and Movement Disorders, 3rd edn. Williams & Wilkins: Baltimore, 1998: 513. 6. Zhernakova A, Withoff S, Wijmenga C. Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Nat Rev Endocrinol 2013; 9: 646–659.
Additional Supporting Information may be found in the online version of this article:
© 2015 EAN
(Pseudo)hemidystonia associated with anti-glutamic acid decarboxylase antibodies – a case report J. Kendaa, M. Kojovic´a, F. Grausb and M. Gregoric Krambergera a
Department of Neurology, University Medical, Center Ljubljana, Ljubljana, Slovenia and bDepartment de Neurologia, Hospital Clı´nic, Barcelona, Spain Correspondence: M. Gregoric Kramberger, Department of Neurology, University Medical Center Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia (tel.: +38615222311; fax: +38615223037; e-mail: [email protected]).
Keywords: anti-GAD antibodies, dystonia, pseudodystonia, stiff person syndrome
a supine position and could perform a few steps with a walker (Video S1). Brain magnetic resonance imaging (MRI) was normal, with no structural lesions in basal ganglia or thalamus. Spinal MRI showed lateral disc herniation at the C6–C7 level with left C7 root compression, presumably resulting from prolonged and fixed neck posture. Baseline cerebrospinal fluid (CSF) analysis was normal, oligoclonal bands were negative. Complete blood count, renal and hepatic function tests, thyroid hormones were normal. Anti-TPO antibodies were highly raised (>1300 kU/l), consistent with the known diagnosis of chronic lymphocytic thyroiditis. Fludeoxyglucose positron emission tomography showed normal metabolism in basal ganglia bilaterally. Anti-neuronal antibodies (anti-Hu, Yo, Ri, CV2, amphiphysin, Ma1, 2) and
neuronal surface antibodies (NMDA, AMPA1, AMPA 2, GABA, LGI1, CASPR2 and GlyR) were negative in serum and CSF. However, a high titer of autoantibodies against glutamic acid decarboxylase (GAD) was detected in both CSF (1:80) and serum (1:10 000). The specific anti-GAD intrathecal index (adjusted to total immunoglobulin G) was 3.3, a value compatible with intrathecal synthesis. Electromyography showed continuous motor unit activity at rest in gastrocnemius and tibialis anterior muscle, paraspinal and neck muscles. She was diagnosed with stiff person syndrome (SPS). Treatment consisted of diazepam (up to 60 mg/day), baclofen (25 mg/day) and intravenous immunoglobulins (0.4 g/kg for 5 days) at 4–6 week intervals. Clinical improvement was noticed: she was able
doi:10.1111/ene.12700 Received: 16 November 2014 Accepted: 6 February 2015 A 55-year-old woman with a history of diabetes mellitus type 1, chronic lymphocytic thyroiditis, vitiligo and no history of head or spine injury presented in May 2013 with abnormal painful posturing of the left hemibody. At the beginning of 2012 she noticed pain between the shoulder blades further progressing to affect the neck. By the end of 2012 her head was tilted to the left, shoulder was elevated and she was unable to straighten her neck. In January 2013 the pain appeared also in her left ankle, which gradually became immobile. On admission she had isolated left hemibody signs with fixed dystonic posture of the neck with left lateral flexion, left shoulder elevation, trunk deviation to the left, fixed left knee and foot plantar flexion (Fig. 1). There was no fluctuation in abnormal body posturing, no sensitivity to external stimuli and no sensory trick. She had no cognitive, psychiatric or cerebellar features to suggest Hashimoto encephalopathy, a disease in which cooccurrence of lymphocytic thyroiditis and dystonia has been described [1]. She needed assistance with standing up from
© 2015 EAN
(b) Fixed dystonic posture of the neck with left lateral flexion and shoulder elevation.
(a) Trunk deviation to the left.
(c) Fixed left knee flexion and foot plantar flexion. Figure 1 Clinical features. (a) Trunk deviation to the left. (b) Fixed dystonic posture of the neck with left lateral flexion and shoulder elevation. (c) Fixed left knee flexion and foot plantar flexion.
1
EUROPEAN JOURNAL OF NEUROLOGY
CASE REPORT
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to move the neck in all directions for 20°–30°, fully extend the knee and make 30° of foot dorsiflexion. However, prolonged (up to 8 week) intervals between infusions resulted in worsening of gait and falls, which eventually resulted in a right hip fracture, followed by intensive rehabilitation. Classical clinical phenotype of antiGAD antibody-positive patients with SPS includes axial stiffness with superimposed episodic spasms and stiff gait. When stiffness is prominent in one leg, it is referred to as the stiff leg syndrome [2]. Our patient is unusual as she presented with abnormal fixed postures in the strict hemi-distribution, first involving neck with left lateral flexion, then trunk and left leg. When facing a patient with hemidystonia, contralateral basal ganglia or thalamic structural lesion should be thought of first [3]. This was excluded in our case. Other considerations, particularly in the presence of painful fixed dystonic posturing, are psychogenic dystonia and pseudodystonia [4,5]. Pseudodystonia refers to abnormal postures of body parts that are not caused by disorders of basal ganglia, e.g. fixed neck postures due to
cranio-vertebral junction disorders, limb contractures complicating spasticity and last but not least SPS [5]. In our patient, the history of diabetes type 1, thyroid disease and vitiligo suggested that she was predisposed to autoimmune disease [6] and thus prompted us to consider SPS and testing for anti-GAD antibodies. Some patients with fixed dystonic postures of the limb(s) or hemi-body (and in the absence of structural brain lesion) may be misdiagnosed as psychogenic if SPS is not considered in the differential diagnosis, particularly when associated with other autoimmune disorders. This is important to recognize because SPS is potentially treatable with immunosuppressive therapy. Disclosure of conflicts of interest The authors declare no financial or other conflicts of interest.
Supporting Information
Video S1. Vitiligo around the eyes is evident. References 1. Tang Y, Chu C, Lin MT, et al. Hashimoto’s encephalopathy mimicking spinocerebellar ataxia. J Neurol 2011; 258: 1705–1707. 2. Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology 2000; 55: 1531–1535. 3. Marsden CD, Obeso J, Zarranz J, Lang A. The anatomical basis of symptomatic hemidystonia. Brain 1985; 108: 463–483. 4. Ganos C, Edwards MJ, Bhatia KP. The phenomenology of functional (psychogenic) dystonia. Mov Disord Clin Pract 2014; 1: 36–44. 5. Jankovic J, Fahn S. Dystonic disorders. In: Jankovic J, Tolosa E, eds. Parkinson’s Disease and Movement Disorders, 3rd edn. Williams & Wilkins: Baltimore, 1998: 513. 6. Zhernakova A, Withoff S, Wijmenga C. Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Nat Rev Endocrinol 2013; 9: 646–659.
Additional Supporting Information may be found in the online version of this article:
© 2015 EAN
![A case of progressive encephalomyelitis with rigidity and positive antiglutamic acid decarboxylase antibodies [corrected].](/assets/img/hold.png)
