Disorders of Ocular Motility with Disease Affecting the Basal Ganglia, Cerebral Cortex, and in Systemic Conditions

This chapter reviews (with illustrative videos) disorders of gaze in diseases involving the basal ganglia, including Parkinson’s disease, progressive supranuclear palsy (PSP), hyperkinetic movement syndromes such as oculogyric crisis, and Huntington’s disease. Ocular motor syndromes caused by lesions in the cerebral hemispheres are discussed, including gaze deviations. Distinctive features of ocular motor apraxia, both acquired and congenital, are highlighted. Eye movements during epilepsy, and abnormal eye movements in patients with dementia, including Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis are reviewed. Eye movement disorders in psychiatric illnesses, including schizophrenia, bipolar affective disorder, and autism are summarized. Eye movements in stupor and coma are discussed. The range of ocular motor disturbances in multiple sclerosis (MS) is reviewed as well as the ocular motor manifestations of metabolic and deficiency disorders, including Niemann-Pick disease, Tay-Sachs disease, Gaucher’s disease, and Wernicke’s encephalopathy. Disorders of eye movements induced by drugs or toxins are tabulated.

Gaze Holding and the Neural Integrator

This chapter reviews the neural network that temporally integrates premotor, velocity-coded signals to achieve tonic contraction of the extraocular muscles to hold the eyes at an eccentric position in the orbits. The mechanical properties of the eye and its supporting tissues are quantified and related to the pulse-slide-step neural command for a saccadic change in eye position. The anatomical substrate and neuropharmacology of the neural integrator is reviewed, including nucleus prepositus hypoglossi, interstitial nucleus of Cajal and cerebellum. Mathematical and animal models for the neural integrator are discussed, addressing points about how a leaky or unstable integrator may arise. Clinical and laboratory evaluation of gaze holding is summarized. Effects of experimentally inactivating the neural integrator are compared with clinical disorders affecting gaze holding, including a discussion of the pathogenesis of gaze-evoked nystagmus and Alexander’s law. Compensatory mechanisms for a leaky neural integrator are discussed, including centripetal, rebound, and gaze-evoked nystagmus.

The Ocular Motor Periphery

This chapter reviews contributions of orbital tissues and extraocular muscles (EOM) to the control of eye movements. The anatomy of the orbit, fascia, fibromuscular pulleys, and EOM are described and related to the kinematics of 3-D eye rotations. Current concepts of the embryology of the EOM and their unique and diverse characteristics are described, suggesting why they are more vulnerable to certain neuromuscular disorders and less susceptible to others, compared with skeletal muscles. Electrophysiological properties of different EOM fiber types (and their motor neuron innervation) are contrasted, describing new models that attempt to account for nonlinear mechanical properties of the orbit. The substrate and roles of extraocular proprioception in the control of eye movements are summarized and related to clinical disorders affecting EOM. The anatomy of the cranial nerves supplying the EOM is summarized, diagrammed and highlighted to aid diagnosis of common palsies of the oculomotor, trochlear, and abducens nerves.

Disorders of Ocular Motility Due to Disease of the Brainstem, Cerebellum, and Diencephalon

This chapter reviews clinical features (with illustrative video cases) and pathophysiology of medullary lesions, including Wallenberg’s syndrome and oculopalatal tremor. Manifestations and pathophysiology of three cerebellar syndromes are described (flocculus and paraflocculus, nodulus and ventral uvula, dorsal vermis and fastigial nucleus), applying these principles to interpret the effects of developmental disorders (e.g., Chiari malformation), hereditary ataxia, paraneoplastic cerebellar degeneration, cerebellar stroke, and cerebellar tumors. Characteristics of pontine lesions are discussed, including lesions of the abducens nucleus, paramedian pontine reticular formation (PPRF), internuclear ophthalmoplegia (INO), one-and-a-half syndrome, slow horizontal saccades, and saccadic oscillations. The effects of midbrain lesions are summarized, including lesions affecting the rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF), interstitial nucleus of Cajal, posterior commissure, and more diffuse processes causing slow vertical saccades or vertical gaze palsy (dorsal midbrain syndrome), including Whipple’s disease. Effects of lesions affecting the superior colliculus, thalamus, and pulvinar are also discussed.

Diagnosis and Management of Vestibular Disorders

This chapter reviews clinical features of eye movement disorders associated with vestibular disorders. The clinical history and examination are reviewed, pointing our key symptoms and signs (with illustrative video cases), for example, in distinguishing vertigo due to stroke from peripheral vestibular disease. Acute vertigo is discussed, including forms due to infections, trauma, and toxins as well as Tullio phenomenon, fistula, canal dehiscence. Recurrent vertigo is reviewed, including Ménière’s syndrome, otosclerosis, inflammatory disorders, migraine, vascular disorders, and epilepsy. The mechanism of hyperventilation-induced vertigo and nystagmus is discussed. Posturally induced vertigo is reviewed, detailing features and treatment of benign paroxysmal positional vertigo (BPPV), and central causes of positional vertigo. The symptom of oscillopsia is reviewed, whether due to an abnormal vestibulo-ocular reflex or paresis of extraocular muscles, or due to nystagmus and other abnormal eye movements. Finally, the topological diagnosis and pathogenesis of skew deviation and the ocular tilt reaction are discussed.

Vergence Eye Movements

This chapter reviews the stimuli for vergence, the properties of fusional and accommodative vergence, as well as vergence made in combination with saccades or vestibular eye movements, or blinks. Different properties of horizontal, vertical, and torsional vergence are discussed. Current models are presented to account for interactions between vergence and saccades. The neural substrate for vergence movements is reviewed from ocular motoneurons to the midbrain supraoculomotor area, to visual cortical areas such as MST and frontal eye field, including pontine nuclei, cerebellar vermis, and fastigial nucleus. Adaptive properties of vergence are reviewed, especially phoria adaptation, discussing the role of the cerebellum. The bedside and laboratory evaluation of vergence is summarized and the pathophysiology of disorders of vergence discussed, including developmental disorders associated with childhood strabismus and acquired disorders such as convergence spasm, convergence insufficiency, vergence forms of nystagmus such as convergence-retraction nystagmus, and effects of focal pontine lesions.

Smooth Visual Tracking and Fixation

This chapter summarizes the properties and neural substrate of smooth eye tracking movements, including visual fixation, smooth pursuit, the ocular following response (OFR), and optokinetic nystagmus (OKN). Fixational eye movements, including microsaccades and drifts, and the role of the OFR in stabilizing gaze are discussed. The properties of pursuit, OFR, and OKN are summarized, including anticipation, prediction, and target selection. The ability of pursuit adaptation to respond to new visual demands is reviewed. Pertinent cortical areas (MT+) and their projections to brainstem and cerebellum are discussed, as well as the accessory optic pathway, and nucleus of the optic tract. Current models for smooth pursuit that incorporate efference copy (corollary discharge), prediction, and Bayesian operators are summarized. Clinical and laboratory evaluation of fixation and visual tracking are reviewed, and the pathogenesis of disorders of these movements discussed, including latent nystagmus accompanying failure to develop binocular vision and infantile nystagmus syndrome.

Diagnosis of Peripheral Ocular Motor Palsies and Strabismus

This chapter reviews the physiologic basis for diplopia, including Sherington’s law of reciprocal innervation and Hering’s law of motor correspondence. Clinical testing is reviewed, including cover tests, red glass, Maddox rod, the Bielschowsky head-tilt test, and abnormal head postures. Clinical features (with illustrative video cases), etiology, and management of abducens nerve palsy, trochlear nerve palsy, oculomotor nerve palsy, and combined neuropathies are discussed, as well as Miller Fisher syndrome, amyotrophic lateral sclerosis, neuromyotonia, Brown’s syndrome and superior oblique myokymia. Disorders of the neuromuscular junction are examined, including systemic botulism, Lambert-Eaton myasthenic syndrome, and myasthenia gravis. Disorders affecting the extraocular muscles are reviewed, including chronic progressive external ophthalmoplegia, Duchenne dystrophy, myotonic dystrophy, oculopharyngeal dystrophy, congenital myopathies, Kearns-Sayre syndrome and mitochondrial myopathies. The chapter also discusses thyroid eye disease, acquired restrictive ophthalmopathies, and congenital cranial dysinnervation disorders (CCDD), Duane syndrome, horizontal gaze palsy with scloliosis, and congenital fibrosis of the extraocular muscles.

The Saccadic System

This chapter reviews the behavioral properties of rapid eye movements, ranging from quick phases of nystagmus to cognitively controlled saccades, and their neural substrate. Properties of various types of saccades are described, including express saccades, memory-guided saccades, antisaccades, and saccades during visual search and reading. Current concepts of regions important for the generation of saccades are reviewed, integrating results of functional imaging and electrophysiology, including brainstem burst neurons and omnipause neurons, the superior colliculus, frontal eye field, supplementary eye field, dorsolateral prefrontal cortex, cingulate cortex, posterior parietal cortex, parietal eye field, thalamus, pulvinar, caudate, substantia nigra pars reticulata, subthalamic nucleus, cerebellar dorsal vermis, and fastigial nucleus. Saccade adaptation to novel visual demands is discussed, and the interaction between saccades and eyelid movements (blinks). Mathematical models of saccades are discussed. Clinical and laboratory evaluation of saccades and the pathophysiology of saccadic disorders, from slow saccades to opsoclonus, are reviewed.

The Vestibular-Optokinetic System

This chapter reviews properties and neural substrate of vestibular and optokinetic eye movements. Geometric aspects of head rotations and translations (linear movements) are related to properties of rotational and translational vestibulo-ocular reflexes. The motion sensors of the vestibular labyrinth -the semicircular canals and otolith organs - are described. The contributions that direct and indirect central pathways make to the direction and temporal properties of vestibulo-ocular responses are summarized. Optokinetic-vestibular interactions during sustained rotations are discussed. Properties of vestibular and optokinetic responses -gain, phase, and time constant - are explained as well as how they are influenced by factors including target location, mental set, and changing visual demands (vestibular adaptation and the cerebellum). The multiple cerebral areas that contribute to vestibular sensation are reviewed. Clinical and laboratory evaluation of vestibulo-ocular function is summarized including rotational and caloric testing, and vestibular-evoked myogenic potentials (VEMPs). The pathogenesis of common vestibular and optokinetic disorders is reviewed.