Stiﬀ person syndrome masquerading as panic attacks PASIEKA/ Science Photo Library
Cyrus S H Ho, Roger C M Ho, Einar P Wilder-Smith
Lancet 2014; 383: 668 Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (C S H Ho MRCPsych, R C M Ho FRCPC), and Division of Neurology, National University Health System, Singapore (Prof E P Wilder-Smith MD) Correspondence to: Dr Cyrus S H Ho, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074 [email protected]
In June, 2012, a 43-year-old Chinese woman came to our clinic with dysphoria, insomnia, and fear of heights. She had no history of mental health problems. The patient had grade 1 L4–L5 spondylolisthesis with lumbar fusion in 2011. Her daughter had died from leukaemia 3 years earlier. The patient was diagnosed with long-term grief, and paroxetine was started. During the next few months she developed panic attacks. When startled by noise, she had painful muscle spasms causing her to momentarily freeze. After titration of antidepressant, her mood improved but panic attacks persisted. In January, 2013, slurred speech, facial asymmetry, and increasing diﬃculty in writing and walking were noted. She had had eight falls in 2 months and two motor vehicle accidents because she could not press the brake. She subsequently required walking aids because of increasing stiﬀness and worsening fear of falling. Her gait was stiﬀ on neurological assessment. There was severe lumbar hyperlordosis, axial stiﬀness, and rigidity. Smooth eye pursuit showed occasional saccadic intrusions in all directions. Arm and leg power was full with normal tone and reﬂexes. Glabellar tap resulted in elicitation of the sternocleidomastoideus tendon reﬂex bilaterally. Results were normal for full blood count, electrolytes, thyroid function, fasting glucose, anti-doublestranded DNA antibodies, antibodies to cardiolipin, and extractable nuclear antigens. Antiglutamic acid decarboxylase (GAD) 65 antibodies were 230 U/mL (normal: <0·9 U/mL). Lumbar puncture was attempted twice under ﬂuoroscopic guidance but failed. Electromyography of paraspinal muscles showed continuous motor unit activity at rest. Blink reﬂex testing showed generalisation with consistent spread to the sternocleidomastoid muscles. Electroencephalography and brain magnetic resonance imaging were normal. The combination of progressive axial rigidity, raised antiGAD 65 antibodies, and characteristic neurophysiological ﬁndings indicative of hyperexcitability of spinal motor neurons led to the diagnosis of stiﬀ person syndrome.1 She had moderate improvement with baclofen 10 mg and alprazolam 0·25 mg thrice daily. After intravenous methylprednisolone (1 g per day for 3 days), her panic attacks resolved and she was able to walk normally by the time she was last reviewed on Aug 20, 2013. Stiﬀ person syndrome is a rare neurological disorder with incidence of one person per million, which often begins insidiously during midlife and aﬀects both sexes. Symptoms arise from deﬁciency of the inhibitory
neurotransmitter γ-aminobutyric acid (GABA), which inhibits spontaneous discharges from spinal motor neurons and is important for motor coordination. 80% of cases are caused by an autoantibody against GAD that inhibits synthesis of GABA. Other autoimmune diseases such as type 1 diabetes mellitus and thyroiditis are often associated. Diagnosis is established by progressive axial muscle rigidity and stiﬀness with painful stimulussensitive spasm, evidence of continuous motor unit activity in axial muscles, and GAD 65 antibodies, in the absence of other neurological disorders. 2 The rarity of stiﬀ person syndrome and non-speciﬁc complaints of stiﬀness with common psychiatric symptoms make diagnosis diﬃcult. On average, the duration from symptom onset to diagnosis ranges from 1 to 18 years, with a mean of 6·2 years.3 Patients are frequently misdiagnosed with psychiatric illness, especially during the early stages of disease when motor disturbances are intermittent while neuropsychiatric symptoms such as paroxysmal fear, exaggerated startle responses to acoustic and tactile stimulation, and emotionally induced spasms are prominent. The most important diﬀerential diagnosis of stiﬀ person syndrome is psychogenic movement disorder, diagnosis of which requires a normal neurological examination, and often shows distractibility and greater than expected improvement from seemingly minor assistance.4 Blink reﬂex testing is always normal in psychogenic movement disorder. The presence of panic attacks or phobias in patients with ﬂuctuating stiﬀness and frequent falls should raise suspicion of stiﬀ person syndrome, since immunosuppressant treatment reduces symptoms and disability.5 Contributors CSHH wrote the manuscript. RCMH and EPW-S looked after the patient and revised the manuscript. Written consent to publish was obtained. References 1 Meinck HM, Thompson PD. Stiﬀ man syndrome and related conditions. Mov Disord 2002; 17: 853–66. 2 Dalakas MC. Stiﬀ person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol 2009; 11: 102–10. 3 Dalakas MC, Fujii M, Li M, et al. The clinical spectrum of anti-GAD antibody-positive patients with stiﬀ-person syndrome. Neurology 2000; 55: 1531–35. 4 Dinnerstein E, Collins D, Berman SA. A patient with post-traumatic stress disorder developing stiﬀ person syndrome. Cogn Behav Neurol 2007; 20: 136–37. 5 Ciccotto G, Blaya M, Kelly RE. Stiﬀ person syndrome. Neurol Clin 2013; 31: 319–28.
Stiff-person syndrome (SPS) is a rare disorder, characterized by progressive fluctuating muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) antibody is primarily involved in the pathogenesis of SPS and SPS is strongly associated with oth
Stiff person syndrome is a highly disabling, progressive autoimmune disorder of the central nervous system characterized by muscle rigidity and spasms. Stiff person syndrome is rare, but is believed to be under diagnosed with only 14 cases been repor