Stiff person syndrome masquerading as panic attacks

Abstract

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 diffi culty 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 stiff ness and worsening fear of falling. Her gait was stiff on neurological assessment. There was severe lumbar hyperlordosis, axial stiff ness, and rigidity. Smooth eye pursuit showed occasional saccadic intrusions in all directions. Arm and leg power was full with normal tone and refl exes. Glabellar tap resulted in elicitation of the sternocleidomastoideus tendon refl ex 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 fl uoroscopic guidance but failed. Electromyography of paraspinal muscles showed continuous motor unit activity at rest. Blink refl ex 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 fi ndings indicative of hyperexcitability of spinal motor neurons led to the diagnosis of stiff person syndrome. 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 aff ects both sexes. Symptoms arise from defi ciency 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 stiff ness 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-specifi c complaints of stiff ness with common psychiatric symptoms make diagnosis diffi cult. On average, the duration from symptom onset to diagnosis ranges from 1 to 18 years, with a mean of 6·2 years. 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 diff erential 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. Blink refl ex testing is always normal in psychogenic movement disorder. The presence of panic attacks or phobias in patients with fl uctuating stiff ness and frequent falls should raise suspicion of stiff person syndrome, since immunosuppressant treatment reduces symptoms and disability.