A Case of Anti-glutamic Acid Decarboxylase-65 Antibody Positive Stiff Person Syndrome Presenting Initially as Acute Peripheral Vestibulopathy, Leading to Delayed Diagnosis After Multiple Hospitalizations

Abstract

Stiff person syndrome (SPS), with a prevalence of one to two per million, is an extremely rare neurological condition that is characterized by axial muscle stiffness and rigidity along with intermittent painful muscle spasms. It is often associated with psychiatric co-morbidities such as anxiety and depression. The pathophysiology, although poorly understood, is widely believed to be autoimmune in nature due to the association of anti-glutamic acid decarboxylase-65 (anti-GAD 65) antibodies with this condition. There is also a paraneoplastic variant that is more commonly associated with anti-ampiphysin antibodies. It occurs most commonly in patients with breast cancer followed by colon cancer. Most of the practising neurologists encounter just one or two cases of SPS in their entire careers, hence this condition remains underdiagnosed, leading to significant disability and distress to the patient. In this case report we describe a postmenopausal female who presented initially with symptoms of vertigo and dizziness and was hospitalized multiple times before the diagnosis was reached. Through this article, we attempt to increase awareness about this condition among practising physicians so as to increase the likelihood of earlier diagnosis and treatment.

An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes

“…Table 1 shows that from 29 studies on breast cancer, six SPSSD subtypes, including classic SPS ( 21 , 30 , 37 – 47 , 50 , 63 , 64 ), SLS ( 57 , 58 , 65 ), paraneoplastic cerebellar degeneration ( 59 ), subacute sensory neuronopathy, subacute cerebellar degeneration ( 60 ), and PERM ( 61 ), among which classic SPS is the major SPSSD subtype, were found to be involved. Patients with breast cancer and PSSD were determined to have other carcinomas, such as colon cancer, non-Hodgkin lymphoma, thymoma and lymphoma, and malignant melanoma ( 21 , 34 , 39 , 41 ). Furthermore, patients with breast cancer and SPSSD were found to have other diseases, including autoimmune diseases, such as paraneoplastic encephalomyelitis, type 1 diabetes, thyroid disease, pernicious anemia, vertigo, psoriasis, thyroid disease, rheumatoid arthritis, sarcoidosis, mixed connective disease, limbic encephalitis, myelopathy, HIV, and ischemic cardiomyopathy ( 21 , 34 , 41 , 45 , 58 , 59 , 65 ).…”

“…The major SPSSD subtype is classic SPS ( 11 , 68 , 69 , 73 , 77 , 80 , 92 – 98 , 134 , 135 ), followed by SPS with myasthenia gravis ( 21 – 25 , 29 , 31 , 34 – 36 , 86 , 89 , 90 , 135 , 136 ), PERM ( 91 ), SLS ( 57 ), progressive dizziness and unstable gait ( 87 ), and NMDAR-SPS ( 9 ), as shown in Table 5 . Moreover, the major carcinoma associated with SPSSD subtypes is breast cancer ( 21 , 39 , 42 , 47 , 50 , 51 , 56 , 57 , 137 ), followed by thymoma ( 11 , 80 , 91 – 98 , 104 – 106 , 134 , 135 ), lymphoma ( 77 , 80 ), lung cancer ( 68 , 69 , 73 ), and other carcinomas ( 21 – 25 , 29 , 31 , 34 – 36 , 86 , 89 , 90 , 135 , 136 ).…”

Bridging the Metabolic Parallels Between Neurological Diseases and Cancer

“…The second disease is stiff-person syndrome (SPS), often seen accompanied by thymomas and breast cancer. SPS is a rare neurological disease with 1-2 cases/million [72,73], and is characterized by rigidity and spasm of skeletal muscles in limbs and trunks. Patients showed increased sensitivity to stimuli, such as noise and emotional perturbation [74].…”

Stiff person syndrome and prior temporal lobectomy: Is it a case of misplaced autoimmunity?

“…One study found high GAD antibody levels in 2.8% of patients with epilepsy, 5 and another study found elevated GAD antibody levels in patients with temporal lobe and generalized epilepsy 6 . Because approximately 60%–80% of SPS patients are positive for anti‐GAD antibodies, clinical diagnosis of SPS may be delayed in patients with underlying seizure disorder 7 . As has been shown in SPS with auditory stimuli causing spells, musicogenic reflex seizures have been described in epilepsy patients with anti‐GAD antibodies, further complicating differentiation between SPS and epilepsy 8 …”

“…6 Because approximately 60%-80% of SPS patients are positive for anti-GAD antibodies, clinical diagnosis of SPS may be delayed in patients with underlying seizure disorder. 7 As has been shown in SPS with auditory stimuli causing spells, musicogenic reflex seizures have been described in epilepsy patients with anti-GAD antibodies, further complicating differentiation between…”