Agoraphobia Secondary to Stiff Person Spectrum Disorder Freeze Attacks

Stiff person spectrum disorder (SPSD) is a rare neuroimmunological condition characterized by central nervous system hyperexcitability. Among the diverse clinical manifestations are “freeze attacks,” which are episodes of sudden, full-body motor inhibition triggered by sensory or emotional stimuli. These episodes differ from the chronic stiffness and spasms typical of SPSD and share features with other conditions such as cataplexy and hyperekplexia. We present a case of agoraphobia that developed in response to freeze attacks.

Case Report

A 43-year-old woman with a history of SPSD, Addison’s disease, type 1 diabetes, and lumbar lordosis but no psychiatric history was referred by her neurologist for treatment of anxiety. Her neurological symptoms began 8 years prior with intermittent foot spasms, later including her leg and truncal muscles. Her muscles would stiffen in response to crowds and startling stimuli. This was both embarrassing and dangerous, as she had several falls with head strike. Laboratory testing was notable for serum glutamic acid decarboxylase 65 (GAD65) antibody (Ab) 243 nmol/L and cerebrospinal fluid (CSF) positive for oligoclonal bands and GAD65 Ab 5.23 nmol/L. This, along with her lumbar lordosis, was consistent with a diagnosis of probable SPSD.¹ Both CSF and serum were negative for amphiphysin, dipeptidyl peptidase–like protein, and glycine receptor Abs.

The patient began to fear having these episodes and developed panic attacks when in crowds or enclosed spaces. She avoided leaving the house, which challenged her ability to care for her children. She reported significant anticipatory anxiety ahead of times she needed to leave her house with ruminative worrying and impaired sleep onset. By the time of initial neurology evaluation, she had been prescribed alprazolam 0.25 mg, which enabled her to leave the house several times a week, though with notable difficulty. She denied anxious tendencies when she could remain at home.

The patient was transitioned from alprazolam to lorazepam 0.5 mg as needed; however, this was less efficacious. Her panic attacks became more frequent, and her avoidance patterns broadened to preclude situations triggering both freeze and panic attacks. She was referred for cognitive-behavioral therapy (CBT) for agoraphobia and panic disorder. Her medications were adjusted to include diazepam 5 mg nightly for leg spasms, fluoxetine 20 mg daily, and alprazolam 0.25 mg twice daily, as needed, for panic attacks. The frequency of her freeze attacks improved after monthly intravenous immunoglobulin, though recurrent episodes near the end of this window are associated with transiently worsened anxiety and avoidant tendencies. She continues under our care.

Discussion

Antibodies against GAD are present in SPSD as well as several other “GAD antibody–spectrum disorders,” including cerebellar ataxia, limbic encephalitis, and autoimmune-associated epilepsy.² Low serum levels are also found in type 1 diabetes² and healthy controls.³ GAD Abs immunoreact with γ-aminobutyric acid (GABA)–ergic neurons and are associated with reduced CSF GABA levels; however, it is unclear whether they are directly pathogenic.²

The freeze attacks in SPSD share characteristics with other disorders with exaggerated startle, including hyperekplexia and cataplexy (though the latter differs in presenting with hypotonia). There is further phenotypic overlap with catatonia and both tonic and dorsal immobility responses.

The nature of these freeze attacks as sudden, unanticipated events with loss of bodily control and potential for harm seems well structured to produce avoidant and fearful responses. Akratic avoidance can be self-perpetuating and lead to significant difficulty meeting functional obligations. Pharmacologic management of the spasms and rigidity of SPSD with benzodiazepines fortuitously offers anxiety benefit; however, close monitoring of these patients for emerging agoraphobia offers the opportunity for early intervention with CBT. There is likely a benefit of treating comorbid generalized anxiety disorder with selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors; however, we are unaware of any clinical trials specifically in this population.

Article Information

Published Online: July 14, 2026. https://doi.org/10.4088/PCC.26cr04185
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(4):26cr04185
Submitted: February 12, 2026; accepted March 20, 2026.
To Cite: Cumming D, Hastreiter G, Abbatemarco J. Agoraphobia secondary to stiff person spectrum disorder freeze attacks. Prim Care Companion CNS Disord 2026;28(4):26cr04185.
Author Affiliations: Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, Ohio (Cumming, Hastreiter); Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, Ohio (Abbatemarco).
Corresponding Author: Drew Cumming, MD, 9500 Euclid Ave, T37, Cleveland OH 44195 ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.
ORCID: Drew Cumming: https://orcid.org/0000-0002-6953-0937;
Gabriel Hastreiter: https://orcid.org/0000-0003-2025-2558;
Justin Abbatemarco: https://orcid.org/0000-0003-1668-4753