This 59-year-old woman had an 8-year history of progressive difficulty with walking, balance, and speech. The earliest reported difficulty was stiffness in her legs and staggering while walking. She tended to walk on the heels with support. She went on to have slurring of speech and difficulties with fine motor skills (eating and getting dressed) by 1 year from the initial gait difficulties. She then developed a left hand resting tremor and dystonia (she misattributed to “arthritis”), which was partially improved on levodopa, although her tremor and her ataxia continued to increase in severity. Given an intercurrent diagnosis of diabetes mellitus type 1, which required insulin, and her prior history of hypothyroidism, antibodies against glutamic acid decarboxylase (GAD) were requested. GAD-65 was 14.2 U/mL (normal range, 0.0 to 1.5). Anti-amphiphysin titers were 6.4 (n < 0.8). Repeat testing confirmed elevated anti-GAD antibodies but were negative for anti-amphiphysin. Brain magnetic resonance imaging (MRI) taken 3 years after symptom onset showed mild to moderate cerebellar atrophy (Fig. 130.1). Full body positron emission tomography (PET) scan was negative for malignancies, intravenous immunoglobulin (IVIG) treatment failed to deliver any benefits. Her condition was compounded by the development of severe orthostatic hypotension. She succumbed to her illness less than 8 years after symptom onset.

Our patient’s relatively rapid progression of ataxia, parkinsonism, dystonia, and hyperreflexia, associated with elevated anti-glutamic acid antibodies, suggested an autoimmune disorder. Her type 1 diabetes and hypothyroidism suggested a pathogenic role for anti-GAD antibodies and the possibility that her deficits fell within the broad spectrum of the stiff person syndrome (SPS). However, further deterioration failed to declare into the typical ascending rigidity of SPS and instead deepened the ataxic phenotype and revealed a clearer olivopontocerebellar pattern of regional atrophy, as shown on a subsequent brain MRI, obtained 6 years after symptom onset (Fig. 130.2). This pattern of atrophy suggested the cerebellar form of multiple system atrophy (MSA-C) or a pseudo-sporadic variant of spinocerebellar ataxia, particularly Spinocerebellar ataxias (SCAs) 2, 3, 12, 17, or 21, whereby parkinsonism is known to emerge as part of the phenotype. Testing for these SCAs was negative.