To describe and present a case series of patients with GlyRα1 antibodies, expanding the clinical spectrum of the disease.

Glycine, an inhibitory neurotransmitter, regulates motor neuron excitability in the central nervous system. Patients with autoantibodies against alpha-1 subunit of the glycine receptor (GlyRα1) present along a spectrum between stiff person syndrome and progressive encephalomyelitis with rigidity and myoclonus (PERM).

Case summaries:

Case 1: A 68-year-old man presented with double vision and torsional multidirectional nystagmus, dysmetria, and dysdiadochokinesia. MRI brain demonstrated mild cerebellar atrophy. Scrotal ultrasound demonstrated 0.9-cm epididymal lesion with differential including an adenomatoid tumor. 

Case 2: A 21-year-old woman presented with diffuse muscle twitching and painful cramps with increased paraspinal muscle tone. She had diffuse myokymic discharges on electromyography.

Case 3: A 71-year-old man presented with exercise-induced whole-body muscle stiffness and increased paraspinal muscle tone. He had abnormal insertional activity on electromyography.

Case 4: A 73-year-old woman presented with downbeat nystagmus (on lateral and downward gaze) and intermittent ocular flutter. MRI brain was normal.  

Case 5: A 35-year-old-woman presented with truncal myoclonic spasms (>100 per day) and hyperekplexia. On exam she had symmetric hyperreflexia and increased tone of abdominal and thoracolumbar paraspinal muscles.

Case 6: A 62-year-old woman presented with pervasive delusions, suicidal ideation, and abnormal eating and sleep patterns. MRI brain demonstrated no abnormality.

Laboratory evaluation:

Serological evaluation demonstrated GlyRα1 antibody positivity in all cases. CSF analyzed in 3/3 patients was normal, of which 2/3 were tested for GlyRα1 antibodies.

Rapid, dramatic clinical response to intravenous immunoglobulin therapy was noted in cases 1-5 and high-dose intravenous steroids in case 6, with maintenance rituximab needed in case 2.

Wide-ranging clinical variability of glycine receptor antibody-mediated neurological syndromes is presented through our case series, with low threshold for diagnostic testing emphasized, as early detection and treatment resulted in good outcomes.