| OCR Text |
Show Multiple System Atrophy: Overview and Neuroophthalmologic features Pavan Vaswani, MD PhD Ali G. Hamedani, MD MHS Learning Objectives • Know the key pathologic features of Multiple System Atrophy • Recognize the clinical presentation, including neuro-ophthalmologic features • Understand the symptomatic therapies and prognosis Definition and Pathophysiology • Eponym: “Shy Drager syndrome” after description in 19601. • MSA also includes striatonigral degeneration and olivopontocerebellar subtypes. • Pathology: Misfolded alpha synuclein in glial cytoplasmic inclusions Glial cytoplasmic inclusions 1Shy and Drager 1960 Arch Neurol "File:MSA Gallays Papp Lantos inclusions.jpg" by Jensflorian is licensed under CC Clinical 1,2 Presentation • Mean onset 53-54.2 years old3, 4 • MSA is one of 4 “atypical parkinsonism” syndromes (as are PSP, CBS, DLB) - patients often present with parkinsonism and other features • Parkinsonism (bradykinesia, rigidity), often symmetric. Tremor less common. (MSA-P = Parkinsonian subtype) • Autonomic insufficiency • • • • • Urinary incontinence or retention Orthostatic hypotension, supine hypertension Gastric motility, constipation (also common in idiopathic PD) Anhidrosis Erectile dysfunction in men • Cerebellar abnormalities (MSA-C = cerebellar subtype) • Ataxia, dysmetria, nystagmus • Laryngeal inspiratory stridor • REM behavior disorder • Dystonia (anterocollis), striatal toe (spontaneous extensor toe response) can also be seen 1Greene 2019 Continuum 3Ben Shlomo et al 1997 Neurology 2Palma et al 2017 Auton Neurosci 4Wenning et al 1994 Brain Camptocormia (stooped posture) seen in parkinsonism Diagnostic criteria (abbreviated and adapted from Gilman et al 20081) DEFINITE MSA: classic neuropathologic findings on post-mortem examination PROBABLE MSA: Onset >30 years old • Autonomic failure with urinary incontinence and erectile dysfunction, OR orthostatic hypotension (30 mmHg systolic or 15mmHg diastolic drop within 3 min), and • Parkinsonism with poor levodopa response (MSA-P), OR Cerebellar syndrome (MSA-C) [Gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction] POSSIBLE MSA: Onset > 30 years old • Parkinsonism OR cerebellar syndrome, and • Dysautonomia: one of urinary frequency, urinary retention, erectile dysfunction, or orthostasis not meeting above criteria, and • One of: • • • • • Upgoing toe with hyperreflexia Stridor Rapidly progressive Parkinsonism Poor levodopa response Postural instability within 3 years of motor symptoms 1Gilman et al 2008 Neurology • • • • • Cerebellar syndrome Dysphagia within 5 years of motor symptoms MRI atrophy in putamen, MCP, pons, or cerebellum FDG PET hypometabolism in putamen, brainstem, or cerebellum Presynaptic nigrostriatal dopaminergic denervation on SPECT or PET Prognosis • Rapid progression as compared to idiopathic PD • Survival ~6.2-9.5 years from diagnosis1, 2 • More than 40% of patients with severe disability or wheelchair bound 5 years after onset2 1Ben Shlomo et al 1997 Neurology 2Wenning et al 1994 Brain Neuro-ophthalmologic features • MSA should be considered in any patient with cerebellar oculomotor findings and parkinsonism or dysautonomia • Saccadic hypometria, impaired pursuits, abnormal VOR suppression (seen to much lesser degree in PD)2 • Cerebellar findings: hypermetric saccades (fastigial involvement), intrusions during pursuits (non-specific), gaze-evoked nystagmus positional downbeat nystagmus • Excessive square wave jerks3 1 Mendoza-Santiesteban et al 2015 Movement Disorders 2 Walsh and Hoyt 2005, pg2526-2527. Available in NOVEL 3 See Table 1 of Anderson et al 2008 Movement Disorders for excellent summary See Fabbrini et al 2011 Movement Disorders for video of eye movements in a patient with MSA Rascol et al 1991 J Neurol Neurosurg Psychiatry Imaging Findings: MRI Brain Cruciform T2 hyperintensity from pontocerebellar degeneration (“hot cross bun” sign) Atrophy of middle cerebellar penducles (MCP sign) Brainstem and cerebellar vermis atrophy Saeed et al 2016 Transl Neurodegener under CC-BY 4.0 Treatment: symptomatic therapy • No disease modifying therapies currently available • Bradykinesia: Carbidopa levodopa or other dopaminergic therapy • Some patients (~29% initially1) have a partial, transient response • Can worsen orthostatic hypotension • Postural hypotension with supine hypertension • Midodrine, fludrocortisone, droxidopa • Elevated head of bed at night • Compression stockings, abdominal binder • Urinary frequency and retention treatment • Physical, Occupational, and Speech therapy 1Wenning et al 1994 Brain |
