The diagnostic value of saccades in movement disorder patients: a practical guide and review

Saccades are rapid eye movements designed to shift the fovea to objects of visual interest. Abnormalities of saccades offer important clues in the diagnosis of a number of movement disorders. In this review, we explore the anatomy of horizontal and vertical saccades, discuss practical aspects of their examination, and review how saccadic abnormalities in hyperkinetic and hypokinetic movement disorders aid in diagnosis, with video demonstration of classic examples. Documentation of the ease of saccade initiation, range of motion and conjugacy of saccades, speed and accuracy of saccades, dynamic saccadic trajectory, and the presence or absence of saccadic intrusions and oscillations are important components of this exam. We also provide a practical algorithm to demonstrate the value of saccades in the differential diagnosis of the movement disorders patient.

[1]  A. Harding.  The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'. , 1982, Brain : a journal of neurology.

[2]  L. Optican,et al.  Saccadic Burst Cell Membrane Dysfunction Is Responsible for Saccadic Oscillations , 2008, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.

[3]  M. Sanders,et al.  Autosomal dominant cerebellar ataxia with pigmentary macular dystrophy. A clinical and genetic study of eight families. , 1994, Brain : a journal of neurology.

[4]  D. Zee,et al.  Vertical supranuclear gaze palsy in Niemann-Pick type C disease , 2012, Neurological Sciences.

[5]  F. Norwood,et al.  Opsoclonus myoclonus syndrome due to squamous cell carcinoma of the oesophagus , 2014, BMJ Case Reports.

[6]  Saumil S. Patel,et al.  Reflexive and volitional saccades: Biomarkers of Huntington disease severity and progression , 2012, Journal of the Neurological Sciences.

[7]  D. Zee,et al.  Ocular motor abnormalities in Huntington's disease , 1997, Vision Research.

[8]  T Nakada,et al.  Oculopalatal myoclonus. , 1986, Brain : a journal of neurology.

[9]  Kathleen E Cullen,et al.  Discharge dynamics of oculomotor neural integrator neurons during conjugate and disjunctive saccades and fixation. , 2003, Journal of neurophysiology.

[10]  D. Zee,et al.  Ocular motor disorders associated with cerebellar lesions: pathophysiology and topical localization. , 1993, Revue neurologique.

[11]  G. Deuschl,et al.  Clinical spectrum and physiology of palatal tremor , 2002, Movement disorders : official journal of the Movement Disorder Society.

[12]  R. Leigh,et al.  Eye movements in parkinsonism , 2000, Neurology.

[13]  H. Ishikawa,et al.  Opsoclonus-myoclonus syndrome following influenza a infection. , 2012, Internal medicine.

[14]  R. Leigh,et al.  EVOLUTION OF OCULOMOTOR AND CLINICAL FINDINGS IN AUTOPSY-PROVEN RICHARDSON SYNDROME , 2009, Neurology.

[15]  Stefano Ramat,et al.  What clinical disorders tell us about the neural control of saccadic eye movements. , 2007, Brain : a journal of neurology.

[16]  J. Bertoni,et al.  Supranuclear gaze palsy in familial Creutzfeldt-Jakob disease. , 1983, Archives of neurology.

[17]  R. Schiffmann,et al.  The Saccadic and Neurological Deficits in Type 3 Gaucher Disease , 2011, PloS one.

[18]  K. Jellinger.  The Neurology of Eye Movements 4th edn. , 2009 .

[19]  Alexandra Durr,et al.  Spinocerebellar ataxia 3 and machado‐joseph disease: Clinical, molecular, and neuropathological features , 1996, Annals of neurology.

[20]  J. Bodensteiner,et al.  Opsoclonus Myoclonus Syndrome Secondary to Epstein-Barr Virus Infection , 1995, Journal of child neurology.

[21]  E. Roullet,et al.  Oculo‐facio‐skeletal myorhythmia as a cerebral complication of systemic Whipple's disease , 1988, Movement disorders : official journal of the Movement Disorder Society.

[22]  L. Schut,et al.  Spinocerebellar ataxia type 8 , 2000, Neurology.

[23]  A. Saykin,et al.  Abnormal error-related antisaccade activation in premanifest and early manifest Huntington disease. , 2011, Neuropsychology.

[24]  J. Grafman,et al.  Eye movements in chorea-acanthocytosis. , 2005, Investigative ophthalmology & visual science.

[25]  R J Leigh,et al.  Applying saccade models to account for oscillations. , 2008, Progress in brain research.

[26]  N. Cairns,et al.  Corticobasal degeneration: an autopsy case clinically diagnosed as progressive supranuclear palsy. , 2000, Clinical neuropathology.

[27]  D. Geschwind,et al.  Late-onset Friedreich ataxia: phenotypic analysis, magnetic resonance imaging findings, and review of the literature. , 2005, Archives of neurology.

[28]  J. Selhorst,et al.  Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple's disease. , 1986, Annals of neurology.

[29]  S. Gielen,et al.  A quantitative analysis of generation of saccadic eye movements by burst neurons. , 1981, Journal of neurophysiology.

[30]  J. Selhorst,et al.  Oculomasticatory myorhythrma: A unique movement disorder occurring in Whipple's disease , 1986 .

[31]  Howard Poizner,et al.  Control of voluntary and reflexive saccades in Parkinson’s disease , 1999, Experimental Brain Research.

[32]  Yanning H. Han,et al.  Abnormalities of optokinetic nystagmus in progressive supranuclear palsy , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[33]  P. Brown,et al.  Familial Creutzfeldt-Jakob disease (codon 200 mutation) with supranuclear palsy. , 1992, JAMA.

[34]  M. Hallett,et al.  Symptomatic and essential palatal tremor. 1. Clinical, physiological and MRI analysis. , 1994, Brain : a journal of neurology.

[35]  R. Leigh,et al.  Pathophysiology of slow vertical saccades in progressive supranuclear palsy , 2001, Neurology.

[36]  R. Leigh,et al.  Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions , 2003, Annals of neurology.

[37]  N. Wadia,et al.  A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families). , 1971, Brain : a journal of neurology.

[38]  R. Marconi,et al.  ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease , 2007, Neurology.

[39]  B. Sandok,et al.  Opsoclonus as the initial manifestation of occult neuroblastoma. , 1971, Archives of ophthalmology.

[40]  S. Folstein,et al.  Abnormal ocular motor control in Huntington's disease , 1983, Neurology.

[41]  T. Turner,et al.  Behavioral Measures of Saccade Latency and Inhibition in Manifest and Premanifest Huntington's Disease , 2011, Journal of motor behavior.

[42]  S. Laroumagne,et al.  “Dancing Eye Syndrome” Secondary to Opsoclonus-Myoclonus Syndrome in Small-Cell Lung Cancer , 2014, Case reports in medicine.

[43]  N. Quinn.  The “round the houses” sign in progressive supranuclear palsy , 1996, Annals of neurology.

[44]  T. Matsushige,et al.  A nationwide survey of opsoclonus–myoclonus syndrome in Japanese children , 2015, Brain and Development.

[45]  D. Robinson,et al.  A hypothetical explanation of saccadic oscillations , 1979, Annals of neurology.

[46]  R. Wurtz,et al.  Saccadic eye movements following injection of lidocaine into the superior colliculus , 2004, Experimental Brain Research.

[47]  D. Tank,et al.  Functional dissection of circuitry in a neural integrator , 2007, Nature Neuroscience.

[48]  R. Leigh,et al.  Dynamic properties of horizontal and vertical eye movements in parkinsonian syndromes , 1996, Annals of neurology.

[49]  Sashank Prasad,et al.  Supranuclear vertical gaze abnormalities in sporadic Creutzfeldt–Jakob disease , 2007, Journal of the Neurological Sciences.

[50]  H. Zoghbi,et al.  Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype , 1998, Neurology.

[51]  D. Droste,et al.  Creutzfeldt-Jakob disease with slow progression. A mimickry of progressive supranuclear palsy. , 2007, Bulletin de la Societe des sciences medicales du Grand-Duche de Luxembourg.

[52]  H. Meinck,et al.  Parainfectious opsoclonus-myoclonus syndrome: high dose intravenous immunoglobulins are effective , 2003, Journal of neurology, neurosurgery, and psychiatry.

[53]  P. Bianchi.  [Whipple's disease]. , 1962, Minerva medica.

[54]  A. Fuchs,et al.  Evidence that the superior colliculus participates in the feedback control of saccadic eye movements. , 2002, Journal of neurophysiology.

[55]  J. Büttner-Ennever,et al.  Premotor neurons for vertical eye movements in the rostral mesencephalon of monkey and human: Histologic identification by parvalbumin immunostaining , 1998, The Journal of comparative neurology.

[56]  J. Cogan,et al.  FIVE TYPES OF EYE MOVEMENT IN THE HORIZONTAL MERIDIAN PLANE OF THE FIELD OF REGARD , 2004 .

[57]  B. Konigsmark,et al.  THE OLIVOPONTOCEREBELLAR ATROPHIES: A REVIEW , 1970, Medicine.

[58]  D. Robinson,et al.  Loss of the neural integrator of the oculomotor system from brain stem lesions in monkey. , 1987, Journal of neurophysiology.

[59]  Christopher Gomez,et al.  Clinical Evaluation of Eye Movements in Spinocerebellar Ataxias: A Prospective Multicenter Study , 2015, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.

[60]  Benjamin Castleman,et al.  Case 47-1968 , 1968 .

[61]  I Litvan,et al.  Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? A clinicopathological study. , 1997, Brain : a journal of neurology.

[62]  P. Beauvais,et al.  Opsoclonus and neuroblastoma. , 1968, The New England journal of medicine.

[63]  H. Wong,et al.  Report of three cases and review of the literature , 2004 .

[64]  R. Leigh,et al.  A Form of Inherited Cerebellar Ataxia with Saccadic Intrusions, Increased Saccadic Speed, Sensory Neuropathy, and Myoclonus , 2002, Annals of the New York Academy of Sciences.

[65]  K. Digre.  Opsoclonus in adults. Report of three cases and review of the literature. , 1986, Archives of neurology.

[66]  G. Solomon,et al.  Opsoclonus and occult neuroblastoma. , 1968, The New England journal of medicine.

[67]  W. Wescoe.  The Reticular Formation , 1962, JAMA.

[68]  R. Baloh,et al.  Eye movements in Friedreich's ataxia. , 1983, Archives of neurology.

[69]  Paul J Tuite,et al.  Progressive ataxia and palatal tremor (PAPT): clinical and MRI assessment with review of palatal tremors. , 2004, Brain : a journal of neurology.

[70]  M. Pless,et al.  Treatment of opsoclonus-myoclonus with highdose intravenous immunoglobulin , 1996, Neurology.

[71]  J. Jankovic,et al.  Neuro-ophthalmic findings in progressive supranuclear palsy. , 1992, Journal of clinical neuro-ophthalmology.

[72]  Simon Hong,et al.  Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity , 2010, Brain : a journal of neurology.

[73]  J. Hort,et al.  FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases , 2011, BMC neurology.

[74]  A. Lees,et al.  MM2 subtype of sporadic Creutzfeldt-Jakob disease may underlie the clinical presentation of progressive supranuclear palsy , 2013, Journal of Neurology.

[75]  A. Taylor,et al.  Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome) is linked to chromosome 9q34. , 2000, American journal of human genetics.

[76]  Aristides B. Arrenberg,et al.  Spatial gradients and multidimensional dynamics in a neural integrator circuit , 2011, Nature Neuroscience.

[77]  Y Suzuki,et al.  Histological identification of premotor neurons for horizontal saccades in monkey and man by parvalbumin immunostaining , 1995, The Journal of comparative neurology.

[78]  R. Tomlinson,et al.  Ocular motor deficits in Parkinson's disease. II. Control of the saccadic and smooth pursuit systems. , 1983, Brain : a journal of neurology.

[79]  S. Rivaud-Pechoux,et al.  Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. , 2003, Brain : a journal of neurology.

[80]  F. Pierelli,et al.  Ataxia with oculomotor apraxia type 2 , 2006, Neurology.

[81]  T. Anderson,et al.  Oculomotor function in multiple system atrophy: Clinical and laboratory features in 30 patients , 2008, Movement disorders : official journal of the Movement Disorder Society.

[82]  A. Singleton,et al.  Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations , 2010, Movement disorders : official journal of the Movement Disorder Society.

[83]  D. Zee,et al.  Gaze fixation deficits and their implication in ataxia–telangiectasia , 2009, Journal of Neurology, Neurosurgery, and Psychiatry.

[84]  R. Yee,et al.  Eye movements in ataxia‐telangiectasia , 1978, Neurology.

[85]  N. Williams,et al.  Perry syndrome due to the DCTN1 G71R mutation: A distinctive levodopa responsive disorder with behavioral syndrome, vertical gaze palsy, and respiratory failure , 2010, Movement disorders : official journal of the Movement Disorder Society.

[86]  F. Andermann,et al.  Ataxia—ocular motor aprilaxia: A syndrome mimicking ataxia‐telangiectasia , 1988 .

[87]  Richard F. Lewis,et al.  Ocular motor abnormalities in ataxia telangiectasia , 1999, Annals of neurology.

[88]  M. Rosenblum,et al.  Immunological and pathological study of anti‐Ri–associated encephalopathy , 1994, Annals of neurology.

[89]  B. Banwell,et al.  Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease , 2014, Neurology.

[90]  W. Dressler,et al.  Report of Three Cases and Review of Literature , 1954 .

[91]  S. Papageorgiou,et al.  A familial case of sleep rhythmic movement disorder persistent into adulthood; approach to pathophysiology , 2011, Movement disorders : official journal of the Movement Disorder Society.

[92]  N. Shimizu.  [Neurology of eye movements]. , 2000, Rinsho shinkeigaku = Clinical neurology.