A man aged 44 years was referred for progressive parkinsonism with poor levodopa response. His medical history comprised unexplained sensory hearing loss, hyperlipidemia, and osteoarthritis. At age 23 years, he had bilateral cataract surgery, and over the last 2 years, he developed worsening stiffness and walking difficulties with frequent falls. He reported features of rapid eye movement (REM) sleep behavior disorder, restless legs syndrome (RLS), visual daytime hallucinations, and rapid cognitive decline. He was given levodopa/benserazide (up to 200 mg/50 mg 4 times daily) without improvement on his Unified Parkinson Disease Rating Scale scores. Therefore, his dopaminergic medication was ceased. Family history was negative for movement or developmental disorders. His neurologic examination showed hypomimia, symmetrical bradykinesia, and rigidity of the extremities without tremors (Video). There was full range of eye movements with large-amplitude saccadic intrusions on smooth pursuit in all directions. Neuropsychological assessment revealed significant abnormalities in cognitive functioning, affecting verbal and nonverbal cognitive skills (ie, speed of information processing, visuospatial skills, verbal and visual memory loss, executive skills). Mini-Mental Status Examination score was 26 of 30 points. Systemic examination was unremarkable. Laboratory and cerebral spinal fluid testing (ie, paraneoplastic antibodies Hu, Yo, Ri, CV2, Ma2, amphiphysin, glutamic acid decarboxylase, N-methyl-d-aspartic acid, LGI1, and Caspr2, 14-3-3 protein) were normal. Cranial magnetic resonance imaging (MRI) showed mild frontal and parietal atrophy. An electroencephalogram demonstrated slowing in keeping with moderate generalized encephalopathy. Total-body positron emission tomography (PET) using fluorine 18 (18F) fluorodeoxyglucose (FDG) as a tracer showed no FDG-avid lesions; however, a subsequent brain-specific FDG-PET/MRI revealed hypometabolism throughout the left cerebral hemisphere and crossed cerebellar diaschisis (Figure 1). As the patient’s cognitive function and parkinsonism had deteriorated rapidly, a brain biopsy of the left frontal cortex was done. Immunohistochemistry showed scattered globular inclusions consistent with Lewy bodies.
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C. Autosomal recessive parkinsonism
In patients with relative subacute onset of cognitive decline and movement disorders, treatable causes must be ruled out. In this patient, central nervous system infection was unlikely owing to normal laboratory and cerebral spinal fluid testing. Paraneoplastic antibody screening was negative, with no malignancies on total-body PET. Newer antibodies against the glycine receptor (GlyR) and immunoglobulinlike cell adhesion molecule 5 (IgLON5) have been discovered that mimic atypical parkinsonian syndromes. Anti-GlyR antibodies are typically associated with stiff-person syndromes or progressive encephalomyelitis with rigidity and myoclonus. Patients with IgLON5 antibodies develop a sleep disorder with parasomnia and/or breathing difficulty with bulbar symptoms, gait abnormalities, oculomotor problems, chorea, and cognitive decline.
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Corresponding Author: Tjerk J. Lagrand, MD, Department of Neurology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, 4102, Brisbane, QLD, Australia (email@example.com).
Published Online: May 9, 2022. doi:10.1001/jamaneurol.2022.0920
Conflict of Interest Disclosures: Dr Lagrand reported receiving grants from the Jan Meerwaldt Foundation for an overseas fellowship during the conduct of the study. No other disclosures were reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
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