Pbl Exam 4 Case 1

These areas are located on either side of the central sulcus.

The primary motor cortex (Brodmann's area 4) is in the precentral gyrus, while the primary somatosensory cortex (Brodmann's areas 3,1 and 2) is in the postcentral gyrus.

Posterior horn is involved mainly in sensory processing

Intermediate horn contains interneurons and certain specialized nuclei.

Anterior horn contains motor neurons.

The white matter is thikest in the cervical levels, where most ascending fibers have already entered the cord and most descending fibers have not yet terminated on their targets.

The sacral cord is mostly gray matter.

The spinal cord has more gray matter at the cervical and lumbosacral levels than at the thoracic levels, particularly in the ventral horns, where lower motor neurons for the arms and legs reside.

Arises from branches of the vertebral arteries and spinal radicular arteries.

The vertebral arteries give rise to the anterior spinal artery that runs along the ventral surface of the spinal cord.

In addition, two posterior spinal arteries arise from the vertebral or posterior inferior cerebellar arteries and supply the dorsal surface of the cord.

The anterior and posterior spinal arteries are variable in prominence at different spinal levels and form a spinal arterial plexus that surrounds the spinal cord.

31 segmental arterial branches enter the spinal canal long its length; most of the branches arise from the aorta and supply the meninges.

Only 6-10 of these reach the spinal cord as radicular arteries, arising at variable levels.

There is usually a prominent radicular artery arising from the left side, anywhere from T5 to L3, but usually between T9 and T12.

This is called the great radicular artery of Adamkiewicz, and provides the major blood supply to the lumbar and sacral cord.

The mid-thoracic region, at approx T4-T8 lies between the lumbar and vertebral arterial supplies and is vulnerable to decreased perfusion.

This region is most susceptible to infarction during thoracic surgery or other conditions causing decreased aortic pressure.

The epidural veins of the spinal cord, called Batson's plexus, do not contain valves, so elevated intra-abdominal pressure can cause reflux of blood carrying metastatic cells (such as prostate cancer) or pelvic infections into the epidural space.

Lesion of the regions of motor association cortex can cause apraxia, in where there is a deficit in higher-order motor planning and execution despite normal strength.

UMNs carry motor system outputs to LMNs located in the spinal cord and brainstem, which in turn, project to muscles in the periphery.

Arise from the cerebral cortex and brainstem. These descending motor pathways can be divided into lateral motor systems and medial motor systems based on their location in the spinal cord.

Lateral motors systems travel in the lateral columns of the spinal cord and synapse on the more lateral groups of ventral horn motor neurons and interneurons.

Include:
1. Lateral corticospinal tract
2. Rubrospinal tract

*Both pathways cross over from their site of origin and descend in the contralateral lateral spinal cord to control contralateral extremities.

Essential for rapid, dextrous movements at individual digits or joints.

Medial motor systems travel in the anteromedial spinal cord columns to synapse on medial ventral horn motor neurons and interneurons.

Include:
1. Anterior corticospinal tract
2. Vestibulospinal tract
3. Reticulospinal tract
4. Tectospinal tract

These pathways control the proximal axial and girdle muscles involved in postural tone, balance, orienting movements of the head and neck, and automatic gait-related movements.

The medial motor systems descend ipsilaterally or bilaterally.

The medial motor systems tend to terminate on interneurons that project to both sides of the spinal cord, controlling movements that involve multiple bilateral spinal segments.

Thus, unilateral lesions of the medial motor systems produce no obvious deficits.

In contrast, lesions of the lateral corticospinal tract produce dramatic deficits.

Role is small is its clinical importance in uncertain, but it may participate in taking over functions after corticospinal injury.

It may also play a role in flexor (decorticate) posturing of the upper extremities, which is typically seen w/lesions above the levels of the red nuclei, in which the rubrospinal tract is spared.

The lateral corticospinal tract.

This pathway controls movement of the extremities, and lesions along its course produce characteristic deficits that often enable precise clinical localization.

About 3% of the corticospinal neurons are giant pyramidal cells called Betz cells, which are the largest neurons in the human nervous system.

Axons from the cerebral cortex enter the upper portions of the cerebral white matter, or corona radiata, and descend toward the internal capsule.

In addition to the corticospinal tract, the cerebral white matter conveys bidirectional information between different cortical areas, and between cortex and deep structures such as the basal ganglia, thalamus, and brainstem.

1. Anterior limb
-separates the head of the caudate from the glubus pallidus and putamen

2. Posterior limb
-separates the thalamus from the glubus pallidus and putamen
-the corticospinal tract lies here*

3. Genu
-is at the transition between the anterior and posterior limbs, at the levels of the foramen of Monro.

Motor fibers for the face are most anterior, and those for the arm and leg are progressively more posterior.

Despite this, the fibers of the internal capsule are compact enough that lesions at this level generally produce weakness of the entire contralateral body (face, arm and leg).

Fibers projecting from the cortex to the brainstem, including motor fibers for the face, are called corticobulbar instead of corticospinal because they project from the cortex to the brainstem, or bulb.

The internal capsule continues into the midbrain cerebral peduncles, meaning literally "feet of the brain".

The white matter is located in the ventral portion of the cerebral peduncles and is called the basis pedunculi.

Contains corticobulbar and corticospinal fibers w/the face, arm, and leg axons arranged from medial t lateral, respectively.

The other portions of the basis pedunculi contain primarily corticopontine fibers.

The corticospinal tract fibers next descend thru the ventral pons, where they form somewhat scattered fascicles. These collect on the ventral surface of the medulla to to form the medullary pyramids.

For this reason the corticospinal tract is sometimes referred to as the pyramidal tract.

The transition from medulla to spinal cord is called the cervicomedullary junction, which occurs at the level of the foramen magnum.

At this point about 85% of the pyramidal tract fibers cross over in the pyramidal decussation to enter the lateral white matter columns of the spinal cord, forming the lateral corticospinal tract.

Anterior horn cells or cranial nerve motor nuclei project directly from the CNS to skeletal muscle.

There is a peripheral synapse located in a ganglion interposed between the CNS and the effector gland or smooth muscle.

The autonomic nervous system itself consists of only efferent pathways

In the intermediolateral cell column in lamina 7 (VII) of spinal cord levels T1 to L2 or L3.

Sympathetic: Norepinephrine

Parasympathetic: Acetylcholine

*One exception to the rule is the sweat glands, which are innervated by sympathetic postganglionic neurons that release acetylcholine

1. Muscle weakness
2. Atrophy
3. Fasciculations
4. Hyporeflexia

Abnormal muscle twitches caused by spontaneous activity in groups of muscle cells.

Muscle weakness and a combination of increased tone and hyperreflexia sometimes referred to as spasticity.

Also seen are abnormal Babinski's sign, Hoffmann's sign, posturing, and so on.

*There may initially be flaccid paralysis w/decreased tone and decreased reflexes, which gradually, over hours or even months, develops into spastic paresis.

Weakness.

Weakness can be caused by lesions or dysfunction at any level in the motor system,

AKA hemiparesis or hemiplegia; pure motor weakness.

Locations ruled in: corticospinal and corticobulbar tract fibers below the cortex and above the medulla: posterior limb of the internal capsule, basis pontis, or middle third of the cerebral peduncle

Side: contralateral to the weakness

Unlikely to be cortical b/c the lesion would have to involve the entire motor strip.

Also unlikely to be muscle or peripheral nerve because in that case conincidental involvement of only half the body would be required.

Also not the spinal cord or medulla b/c in that case the face would be spared.

1. Lacunar infarct of the internal capsule or of the pons
2. Infarct of the cerebral peduncle

1. Upper motor neuron signs are usually present

2. Dysarthria (dysarthria-pure motor hemiparesis)

3. Ataxia (ataxia-hemiparesis)

Ruled in: entire primar motor cortex, including face, arm, and leg representations of the precentral gyrus, or corticospinal and corticobulbar tract fibers above the medulla.

Side: Contralateral to the weakness

Unlikely to be below the medulla

Numerous, including infarct, hemorrhage, tumor, trauma, herniation, post-ictal state, and so on...

AKA hemiplegia or hemiparesis sparing the face

Location: Arm and leg area of the motor cortex; corticospinal tract from the lower medulla to the C5 level of cervical spinal cord

Side:
-Motor cortex or medulla: contralateral to the weakness
-Cervical spinal cord: ispilateral to weakness

Unlikely to be the corticospinal tract below the motor cortex above the medulla b/c the corticobulbar tract fibers are very nearby, and the face would thus usually be involved.

Unlikely to be muscle or peripheral nerve b/c in that case coincidental involvement of only half of the body would be required.

Also, not below C5 in the cervical cord b/c in that case some arm muscles would be spared.

Upper motor neuron signs are usually present. Cortical lesions sparing the face are often in a watershed distribution, and they affect proximal more than distal muscle (man in the barrel syndrome).

Cortical lesions may be associated w/aphasia or hemineglect. In medial medullarly lesions there may be loss of vibration and joint position sense on the same side as the weakness, and tongue weakness on the opposite side.

In lesions of the spinal cord, the Brown-Sequard syndrome may be present.

1. Watershed infarct (anterior cerebral-middle cerebral watershed)
2. Medial or combined medial and lateral medullary infarcts
3. Multiple sclerosis
4. Lateral trauma
5. Compression of the cervical spinal cord.

AKA faciobrachial paresis or plegia.

Location: face and arm areas of the primary motor cortex, over the lateral frontal convexity.

Side: Contralateral to weakness

Ruled out: Unlikely to be muscle or peripheral nerve b/c in that case coincidental involvement of the face and arm would be required. Uncommon in lesions at the internal capsule or below b/c the corticobulbar and corticospinal tracts are fairly compact, resulting in leg involvement w/most lesions

Upper motor neuron signs and dysarthria are usually present.

In dominant-hemisphere lesions, Broca's aphasia is common; in non dominant-hemisphere lesions, hemineglect may occasionally be present.

Sensory loss can occur if the lesion extends into the parietal lobe.

Middle cerebral artery superior division infarct is the classic cause.

Tumor, abscess, or other lesions may also occur in this location.

AKA Brachial monoparesis or monoplegia

Arm area of primary motor cortex, or pheripheral nerves supplying the arm

Side:
-Motor cortex: contralateral to weakness
-Peripheral nerves: ipsilateral to weakness

Ruled out: Unlikely, anywhere along the corticospinal tract, b/c in that case the face and/or lower extremity would also likely be involved.

Rare cases of foramen magnum tumors may initially affect one arm.

There may be associated upper motor neuron signs, cortical sensory loss, aphasia, or subtle involvement of the face or leg.

Occasionally none of these are present. The weakness pattern may be incompatible w/a lesion of peripheral nerves.

For example, marked weakness of all finger, hand, and wrist muscles w/no sensory loss and normal proximal strength does not occur w/peripheral nerve lesions.

There may be associated lower motor neuron signs.

Weakness and sensory loss may be compatible w/a known pattern for a peripheral nerve lesion.

Motor cortex lesion: infarct of a small cortical branch of the middle cerebral artery, or a small tumor, abscess, or the like.

Peripheral nerve lesion: compression injury, diabetic neuropathy, and so on.

AKA crural monoparesis or monoplegia

Leg are of the primary motor cortex along the medial surface of the frontal lobe, lateral corticospinal tract below T1 in the spinal cord, or peripheral nerves supply the leg.

Side: Contralateral to weakness if lesion in motor cortex; ipsilateral if spinal cord or peripheral nerve lesion.

Ruled out: Unlikely to be in the corticospinal tract above the upper thoracic cord, b/c in that case the face and or upper extremity would usually also be involved.

Rarely, cervical cord tumors can initially cause leg weakness only.

There may be associated upper motor neuron signs, cortical sensory loss, frontal lobe signs such as a grasp reflex, or subtle involvement of the arm or face.

Occasionally none of these are present. The weakness pattern may be incompatible w/a lesion of the peripheral nerves - for example, diffuse weakness of all muscles in one leg.

There may be associated upper motor neuron signs, a Brown-Sequard syndrome, a sensory level, or some subtle spasticity of the contralateral leg. Sphincter function may be involved.

The weakness pattern may be incompatible w/a lesion of the peripheral nerves.

There may be associated lower motor neuron signs.

Weakness and sensory loss may be compatible w/a known pattern for a peripheral nerve lesion.

Motor cortex lesion: infarct in the anterior cerebral artery territory, or a small tumor, abscess, etc..

Spinal cord lesion: unilateral cord trauma, compression by tumor, multiple sclerosis

Peripheral nerve lesion: compression injury, diabetic neuropathy, etc...

AKA Bell's palsy (peripheral nerve); isolated facial weakness

Common: peripheral facial nerve (CN VII)

Uncommon: lesions in the face area of the primary motor cortex or in the genu of the internal capsule; facial nucleus and exiting the nerve fascicles in the pons or rostral lateral medulla.

Ruled out: Unlikely w/lesions below the rostral medulla

The forehead and orbicularis oculi are not spared. With facial nerve lesions (e.g. Bells) there may be hyperacusis, decreased taste, and pain behind the ear on the affected side.

In facial nucleus lesions in the pons there are usually deficits associated w/damage to nearby nuclei and pathways such as CN VI, CN V, or the corticospinal tract.

In rostral lateral medullary lesions, a lateral medullary syndrome will be present.

The forehead is relatively spared.

Dysarthria and unilateral tongue weakness are common. There may be subtle arm involvement.

In cortical lesions, sensory loss or aphasia may be present.

Facial nerve: Bell's palsy, trauma, surgery.

Motor cortex, capsular genu, pons, or medula: infarct.

Facial weakness may be difficult to detect in cases in which it occurs bilaterally, called facial diplegia, since the weakness is symmetrical.

Causes include motor neuron disease, bilateral peripheral nerve lesions (such as in Guillain-Barre syndrome or in bilateral Bell's palsy), or bilateral white matter abnormalities caused by ischemia or demyelination (such as in pseudobulbar palsy).

AKA brachial diplegia

Medial fibers of both lateral corticospinal tracts; bilateral cervical spine ventral horn cells; peripheral nerve or muscle disorders affecting both arms.

Ruled out: Unlikely to be in the corticospinal tract b/c in that case the face and/or legs would also be involved.

A central cord syndrome or anterior cord syndrome may be present.

Central cord syndrome:
1. Syringomyelia
2. Intrinsic spinal cord tumor
3. Myelitis

Anterior cord syndrome:
1. Anterior spinal artery infarct
2. Trauma
3. Myelitis

Peripheral nerve:
1. Bilateral carpal tunnel syndrome
2. Disc herniations

AKA Paraparesis or paraplegia

Bilateral leg areas of the primary motor cortex along the medial surface of the frontal lobes

Lateral corticospinal tracts below T1 in the spinal cord

Cauda equina syndrome or other peripheral nerve or muscle disorders affecting both legs.

Ruled out: unlikely to be in the corticospinal tracts above the upper thoracic cord, b/c in that case the face and/or upper extremities would also be involved.

Rarely, cervical cord tumors can initially cause bilateral leg weakness w/o arm involvement.

Upper motor neuron signs may be present.

There may also be frontal lobe dysfunction, including confusion, apathy, grasp reflexes, and incontinence.

Upper motor neuron signs, sphincter dysfunction, and autonomic dysfunction may be present.

A sensory level or loss of specific reflexes may also help to determine the segmental level of the lesion.

Cauda equina syndrome is associated w/sphincter and erectile dysfunction, sensory loss in lumbar or sacral dermatomes, and lower motor neuron signs.

Distal symmetrical polyneuropathies tend to preferentially affect distal muscles, and may have associated distal "glove-stocking" sensory loss and lower motor neuron signs.

Neuromuscular disorders and myopathies often affect proximal more than distal muscles.

Bilateral medial frontal lesions:
-parasagital meningioma
-bilateral anterior cerebral artery infarcts
-cerebral palsy

Spinal cord lesions: numerous, including tumor, trauma, myelitis

Cauda equina syndrome:
-tumor, trauma disc herniation

Other peripheral nerve or muscle disorders:
-The lower extremities are often clinically affected before the arms in Guillain-Barre syndrome
-Lambert-Eaton syndrome
-numerous muscle disorders
-distal symmetrical polyneuropathies (caused by diabetes and other toxic, metabolic, congenital and inflammatory conditions).

AKA quadriparesis, quadriplegia, tetraparesis, tetraplegia

Bilateral arm and leg areas of the motor cortex; bilateral elsions of the corticospinal tracts from the lower medulla to C5.

Peripheral nerve motor neuron or muscle disorders severe enough to affect all four limbs usually also affect the face, although in some cases face involvement may be relatively mild.

Unlikely to be below the motor cortex and above the medulla b/c the face would then be involved.

Unlikely to be in the spinal cord below C5 b/c the arms would then be partly spared.

Cortical lesions sparing the face are often in a watershed distribution and affect proximal more than distal muscles (man in the barrel syndrome).

Upper motor neuron signs are usually present and there may be associated aphasia, neglect, or other cognitive disturbances.

Upper motor neuron signs are usually present.

There may be a sensory level, sphincter dysfunction, or autonomic dysfunction.

High cervical lesions may cause respiratory weakness and may involve the spinal trigeminal nucleus, causing decreased facial sensation.

Upper motor neuron signs are usually present.

There may be occipital headache, tongue weakness, sensory loss, hiccups, respiratory weakness, autonomic dysfunction, sphincter dysfunction, or abnormal eye movements.

Motor cortex lesions:
-bilateral watershed infarcts (anterior cerebral-middle cerebral watershed)

Upper cervical cord and lower medullary lesions:
-tumor
-infarct
-trauma
-MS

Peripheral nerve or muscle disorders: numerous

Bilateral lesions of the entire motor cortex; bilateral lesions of the corticospinal and corticobulbar tracts anywhere from corona radiata to pons; diffuse disorders involving all lower motor neurons, peripheral axons, neuromuscular junctions, or muscles.

Small focal or unilateral lesions do not produce generalized weakness.

Lesions of the lower medulla or spinal cord spare the face or upper extremities.

Bilateral cerebral or corticospinal lesions may be associated w/upper motor neuron signs.

Lesions of the peripheral nerves may be associated w/lower motor neuron signs.

Sensory loss, eye movement abnormalities, pupillary abnormalities, autonomic disturbances, or impaired consciousness may be present, and these features help determine the location and nature of the lesion.

Respiratory depression is common w/sever generalized weakness.

Global cerebral anoxia, pontine infarct or hemorrhage, advanced amyotrophic lateral sclerosis, Guillain-Barre syndrome, myasthenia, botulism, and numerous other diffuse neoplastic, infectious, inflammatory, traumatic, toxic, or metabolic disturbances.

Unilateral or bilateral

Stiff-legged circumduction, sometimes with scissoring of the legs and toe-walking (form increased tone in calf muscles), decreased arm swing unsteady, falling toward side of greater spasticity.

Unilateral or bilateral corticospinal tract

Causes:
-cortical, subcortical, or brainstem infarcts affecting upper motor neuron pathways
-cerebral palsy
-degenerative conditions
-multiple sclerosis
-spinal cord lesions

Wide based, unsteady, staggering side to side, and falling toward side of worse pathology.

Subtle deficit can be detected with tandem hell-to-to gait testing.

Cerebellar vermis or other midline cerebellar structures

Causes:
-toxins such as alcohol
-tumors of cerebellar vermis
-infarcts or ischemia of cerebellar pathways
-cerebellar degeneration

Looks similar to ataxic gait, wide based and unsteady.

Patients sway and fall when attempting to stand w/feet together and eyes closed (Romberg sign)

Vestibular nuclei, vestibular nerve, or semicircular canals

Causes:
-toxins such as alcohol
-infarcts or ischemia of vestibular nuclei
-benign positional vertigo
-Meniere's disease

Slow, shuffling, narrow or wide based, magnetic, unsteady.

Sometimes resembles Parkinsonian gait.

Some patients can perform cycling movements on their back much better than they can walk, giving rise to the term "gait apraxia" in this condition

Frontal lobes or frontal subcortical white matter

Causes:
-hydrocephalus
-frontal tumors such as glioblastoma or meningioma
-bilateral anterior cerebral artery infarcts
-diffuse subcortical white matter disease

Slow, shuffling, narrow based.

Difficulty initiating walking. Often stooped forward, with decreased arm swing, and "en bloc turning".

Unsteady, with retropulsion, taking several rapid steps to regain balance when pushed backward

Substantia nigra or other regions of basal ganglia

Causes:
-Parkinson's disease
-other parkinsonian syndromes, such as progressive supranuclear palsy, or use of neuroleptic drugs.

Unilateral or bilateral dance-like (choreic), flinging, or writhing movements occur during walking and may be accompanied by some unsteadiness.

Subthalamic nucleus, or other regions of basal ganglia

Causes:
-Huntington's disease
-infarct of subthalamic nucleus or striatum
-side effect of levodopa
-other familial or drug-induced dyskinesias

High-stepping, foot flapping gait, with particular difficult walking in the dark or on uneven surfaces.

Patients sway and fall in attempts to stand with feet together and eyes closed (Romberg sign).

Posterior columns or sensory nerve fibers

Causes:
-posterior cord syndrome
-severe sensory neuropathy

Exact appearance depends on location of lesion.

With proximal hip weakness there may be a waddling, Trendelenburg gait.

Severe thigh weakness may cause sudden knee buckling.

Foot drop can cause a high-stepping, slapping gait with frequent tripping.

Nerve roots, peripheral nerves, neuromuscular junction, or muscles.

Causes:
Numerous peripheral nerve and muscle disorders.

Can be hard to diagnose. Sometimes patients say they have poor balance, yet spontaneously perform highly destabilizing swaying movements while walking, without ever falling.

Localization: psychologically based

Causes: conversion disorder or factitious disorder.

An autoimmune inflammatory disorder affecting CNS system myelin.

The cause is unknown, although there is mounting evidence that T lymphocytes may be triggered by a combination of genetic and environmental factors to react against oligodendroglial myelin. Myelin in the peripheral nervous system is not affected.

Multiple plaques of demyelination and inflammatory response can appear and disappear in multiple locations in the CNS over time, eventually forming sclerotic glial scars.

Demyelination causes slowed conduction velocity, dispersion or loss of coherence of action potential volleys, and ultimately conduction block.

B/c dispersion increases w/temp, some patients have worse symptoms when they are warm.

about .1% in the US, witha higher worldwide prevalence in whites from northern climates, and about a 2:1 female to male ratio.

Lifetime risk of developing MS goes up 3-5% if a first degree relative is affected. Peak age of onset is 20-40 years. Onset before 10 or after 60 is rare but not unheard of.

Two or more deficits separated in neuroanatomical space and time.

In practice, the Dx is based on the presence of typical clinical features, together with MRI evidence of white matter lesions, slowed conduction velocities on evoked potentials, and the presence of oligoclonal bands in CSF obtained via lumbar puncture.

Abnormal discrete bands seen on CSF gel electrophoresis.

They result from the synthesis of large amounts of relatively homogeneous immunoglobulin by individual plasma cell clones in the CSF.

These bands are present in over 85% of patients with clinically definite MS.

MRI finding suggestive of MS include multiple T2-bright areas, representing demyelinative plaques located in the white matter.

The plaques tend to extend into the white matter from periventricular locations, and they occur in both supratentorial and infratentorial structures.

Characterized by gradually progressive degeneration of both upper motor neurons and lower motor neurons, leading eventually to respiratory failure and death.

ALS has an incidence of 1-3 per 100,000 and is slightly more common in men. The usual age of onset is in the 50-60's. Most cases occur sporadically, but there are also inherited forms that can have autosomal dominant, recessive, or X-linked transmission.

Usualy weakness or clumsiness, which often begins focally and then spreads to involve adjacent muscle groups.

Painful msucel cramping and fasciculations are also common. Some patients present with dysarthria, and dysphagia, or with respiratory symptoms.

A head droop is often present b/c of weakness of the neck muscles.

Spinal muscular atrophy occurring in infancy is known as Werdnig-Hoffmann disease and usually leads to death by the second year of life.

Dx: Embolic infarct of the left precentral gyrus.

Dx: Right precentral gyrus, primary motor cortex, leg area - infarct.

Most likely caused by peripehral lesions of the facial nerve; however, presence of mild dysarthria and finger curling suggests invovlement of the corticobulbar and corticospinal tracts as well.

Dx: infarct of the left precentral gyrus face area.

Dx: right corticobulbar and corticospinal tracts in the posterior limb of the internal capsule or ventral pons.

Possible MS

Dx: Lacunar infarction in left corticobulbar and corticospinal tracts in the posterior limb of the internal capsule or ventral pons.

Involve the brainstem nuclei of CN III, IV, and VI; the peripheral nerves arising from these nuclei; and the eye movement muscles

Involve brainstem and forebrain circuits that control eye moments thru connections w/the nuclei of CN III, IV, and VI.

1. Lateral rectus CN VI
2. Media rectus CN III
3. Superior rectus CN III
4. Inferior rectus CN III
5. Superior oblique CN IV
6. Inferior oblique CN III

Causes elevation and intorsion of eye

Causes depression and extorsion of eye

Elevation and extorsion; elevation increases w/adduction and extorsion increases with abduction

Depression and intorsion; depression increases with adduction; intorsion increases w/abduction

1. Levator palpebrae superior
2. Pupillary constrictor
3. Dilator muscles
4. Ciliary muscle

Superior: superior rectus and levator palpebrae superioris

Inferior: Medial rectus, inferior rectus, and inferior oblique

*Also carries preganglionic parasympathetic fibers to the pupillary constrictor muscles of the eye and ciliary muscles of the lens.

Located in the upper midbrian at the level of the superior colliculi and red nuclei, just ventral to the periaqueductal gray matter.

Fascicles of the occulomotor nerve exit the brainstem as CN III in the interpeduncular fossa between the posterior cerebral and superior cerebellar arteries.

Contain preganglionic parasympathetic fibers, form a V shape as they curve over the dorsal aspect of the oculomotor nuclei and fuse anteriorly in the midline.

The parasympathetic fibers controlling pupil constriction run in the superficial portion of the oculomotor nerve as it travels in the subarachnoid space, and they are susceptible to compression from aneurysms, particularly arising from the nearby posterior communicating artery.

1. Unilateral weakness of the levator palpebrae superior, or unilateral pupillary dilation, cannot arise from unilateral lesions of the oculomotor nucleus.

2. Lesions of the oculomotor nucleus affect the contralateral superior rectus.

Lesions of the oculomotor nucleus will actually affect the ipsilateral superior rectus since the crossing fibers traverse the oculomotor nucleus before exiting the third nerve fascicles.

Located in the lower midbrain at the level of the inferior colliculi and the decussation of the superior cerebellar peduncle.

Like the oculomotor nuclei, they lie just ventral to the periaqueductal gray matter and are bounded ventrally by the fibers of the medial longitudinal fasciculus.

The trochlear nerves are the only cranial nerves to exit the brain dorsally. Also, unlike any other cranial nerve, the trochlear nerves exit the brainstem in a completely crossed fashion.

The are very thin and are relatively easily damaged by shear injury from head trauma.

They travel through the subarachnoid space along the underside of the tentorium cerebelli and then enter the cavernous sinus to reach the orbit via the superior orbital fissure, and they innervate the superior oblique muscles.

Lie on the floor of the fourth ventricle under the facial colliculi in the mid to lower pons.

Abducens fibers travel ventrallly to exit at the pontomedullary junction. The abducens nerve must then follow a long course in the subarachnoid space, ascending between the pons and clivus

The abducens nerve then exits the dura to enter Dorello's canal, running between the dura and skull, under the petroclinoid ligament.

It next makes a sharp bend as it passes over the petrous tip of the temporal bone to reach the cavernous sinus.

This long vertical course may explain why the abduncens nerve is highly susceptible to downward traction injury produced by elevated intracranial pressure.

After traversing the cavernous sinus, the abducens nerve enters the orbit via the superior orbital fissure to innervate the lateral rectus muscle.

1. Mechanical problems such as orbital fracture with muscle entrapment
2. Disorders of the extraocular muscles such as thyroid disease, or orbital myositis
3. Disorders of the neuromuscular junction such as myastenia gravis
4. Disorders of CN III, IV, VI, and their central pathways.
5. Disorders involving the supranuclear oculomotor pathways such as internuclear opthalmoplegia, skew deviation, and ingestion of toxins such as EtOH or anticonvulsants

1. Did the diplopia go away when the patient closed or covered one eye?
-suggests it was caused by an eye movement abnormality

2. Did the diplopia get worse with near or far objects, when looking up or down or to the left or right?
-This info can help localize the cause

When an extraocular muscle is not working properly, dysconjugate gaze results, causing diplopia.

A helpful rule of thumb is that the image farther toward the direction of gaze is always the one seen in the abnormal eye.

For example, when looking at an object to the right, if one eye does not move to the right then it will form a second image that appears displaced to the right.

Can also be helpful in examining patients w/diplopia.

A transparent piece of red glass or plastic is held over one eye, ususally the right, and a small white light is held directly in front of the patient. The image seen by the right eye is therefore red, and the image seen by the left is white.

The patient is then asked to follow the light as it is moved to nine different positions of gaze, and to report o the locations of the white and red images.

Normally, the white and red images are fused in all positions of gaze.

Exotropia: Abnormal lateral deviation of one eye

Esotropia: Abnormal medial deviation

Vertical deviation is usually described only with respect to the eye that is higher, and it is called hypertropia.

Another helpful test for subtle eye muscle weakness is the cover-uncover test.

Visual input normally helps maintain the eyes yoked in the same direction. Therefore, when an eye is covered while looking in the direction of a weak muscle, it may drift slightly back toward the neutral position.

Mild weakness present only with an eye covered is called a phoria, in contrast to a tropia.

In young children, b/c the visual pathways are still developing, congenital eye muscle weakness can produce strabismus (dysconjugate gaze) that over time causes suppression of one of the images, resulting in amblyopia (decreased vision in one eye). For this reason, early intervention is essential.

Causes paralysis of all extraocular muscles except for the lateral rectus and superior oblique.

Therefore, the only remaining movements of the eye are some abduction and some depression and intorsion.

B/c of decreased tone in all muscles except the lateral rectus and superior oblique, the eye may come to lie in a "down and out" position at rest. In addition, paralysis of the levator palpebrae superior causes the eye to be closed (complete ptosis) unless the upper lid is raised with a finger.

Also, the pupil is dilated and unresponsive to light b/c of involvement of the parasympathetic fibers that run w/the oculomotor nerve.

Someone with oculomotor palsy, the patient may report that the diplopia is worse when looking at near objects and better when looking at distant objects, since convergence is impaired.

Red glass testing in the third-nerve palsy generally reveals diagonal diplopia that is most severe when looking up and medially with the affected eye.

Diabetic neuropathy or head trauma in which shearing forces damage the nerve.

Another important cause is compression of the nerve by intracranial aneurysms, most often arising from the junction of the Pcomm with the internal carotid artery.

Can also be damaged by other abnormalities in the subarachnoid space, cavernous sinus, or orbit.

Herniation of the medial temporal lobe can compress the nerve.

Opthalmoplegic migraine is a condition usually seen in children that causes reversible oculomotor nerve palsy.

Left eye would be down and out, and the left eye would be closed unless the upper lid is raised with a finger.

The left pupil would be dilated and unresponsive to light.

Since aneurysms can cause life-threatening intracranial hemorrhage, there should be a high index of suspicion for aneurysms in patients presenting w/third nerve palsy.

Aneurysms classically cause a painful oculomotor palsy that involves the pupil.

These patients should be considered to have a PComm aneurysm unless proven otherwise.

Complete oculomotor palsy that spares the pupil is not caused by aneurysms; it is usually caused by diabetes.

The reason is though to be that the parasympathetic fibers are located near the surface of the nerve, and if the nerve compression is severe enough to cause complete paralysis of the muscles innervated by CN III, then the pupillary fibers should be involved as well.

Could be caused by partial compression of CN III by an aneurysm, so an angiogram is usually necessary.

Can sometimes affect the superior division or inferior division in isolation.

A lesion of the superior division causes weakness of the superior rectus and levator palpebrae superior, production so-called double elevator palsy.

The trochlear nerve produces depression and intorsion of the eye.

Therefore, in trochlear nerve palsy there is vertical diplopia.

If the weakness is severe, the affected eye may show hypertropia.

There may also be extorsion of the eye, which is not usually visible to the examiner.

Patients w/ CN IV palsy often report that they can improve the diplopia by looking up (chin tuck) and by tilting the head away from the affected eye b/c these maneuvers compensate for the hypertropia and extorsion, respectively.

The vertical diplopia is most severe when the affected eye is looking downward and toward the nose, which can be confirmed w/red glass testing.

1. The affected eye has hypertropia

2. Vertical diplopia worsens when the affected eye looks nasally

3. Vertical diplopia improves with head tilt away from the affected eye

4. Vertical diplopia worsens with downgaze

Have the patients look at a horizontal line.

In a trochlear nerve palsy, the patient will see two lines, with the lower line tilted.

These two lines form an arrowhead with the "point" directed toward the affected side.

The head movement is always in the direction of action normally served by the affected muscle.

For example, in a right trochlear palsy the head is held down and tilted to the left; the normal action of the right trochlear nerve is depression and intorsion of the eye.

The head would be tilted to the right, chin tucked and looking up, and the affected eye would show hypertropia.

The trochlear nerve is the most commonly injured cranial nerve in head trauma, probably b/c of its long course and thin caliber, making it susceptible to shear injury.

Head trauma, and other causes, such as CN IV pathology in the subarachnoid space, cavernous sinus, or orbit include neoplasm, infection and aneurysms.

In many cases the cause remains unknown, and these cases may be caused by microvascular damage to the nerve, esp in diabetic patients.

Vascular or neoplastic disorders within the midbrain or near the tectum can also affect the trochlear nuclei or nerve fascicles.

1. Disorders of extraoxcular muscles
2. Myasthenia gravis
3. Lesions of the superior division of the oculomotor nerve affecting the superior rectus
4. Skew deviation

Defined as vertical disparity in the position of the eyes of supranuclear origin.

Unlike trochlear palsy, in skew deviation the vertical disparity is typically (but not always) relatively constant in all positions of gaze.

Skew deviation can be caused by lesions of the cerebellum, brainstem, or even the inner ear.

1. Cerebellar lesions
2. Meningitis
3. Incipient tonsillar herniation
4. Torticollis

Horizontal diplopia.

In some cases esotropia of the affected eye may be present as well.

In contrast to third-nerve palsy, patients report that the diplopia is better when they are viewing near objects and worse when they are viewing far objects.

On examination, the affected eye does not abduct normally. In milder abducens nerve palsy these may simply be incomplete "burial of the sclera" on lateral gaze.

Diplopia worsens when the patient tries to abduct the affected eye, which can be confirmed by red glass testing.

Some patients may tend to turn the head toward the affected eye in an effect to compensate for the diplopia.

B/c of its long course along the clivus and over the sharp ridge of the petrous temporal bone, the abducens nerve is particularly susceptible to injury from downward traction caused by elevated ICP.

Abducens palsy is therefore an important early sign of supratentorial or infratentorial tumors, pseudotumor cerebri, hydrocephalus, and other intracranial lesions.

Damage to CN VI can occur in the subarachnoid space, sinus, or orbit.

Common disorders include head trauma, infection, neoplasm, inflammation, aneurysms, and cavernous sinus thrombosis.

Can also result from microvascular neuropathy like that seen in diabetes.

Cause weakness of ipsilateral eye abduction resembling a peripheral abducens nerve lesion.

However, lesions of the abducens nucleus in the pons produce not a simple abducens palsy, but instead a horizontal gaze palsy in the direction of the lesion.

Additionally, lesions of the abducens nucleus often affect the nearby fibers of CN VII in the facial colliculus, resulting in a ipsilateral facial weakness.

Movements of BOTH eyes in one direction are decreased.

Myasthenia gravis and disorders of the extraocular muscles caused by thyroid disease, tumors, inflammation, or orbital trauma.

Light entering one eye activates retinal ganglion cells, which project to both optic tracts b/c of fibers crossing over in the optic chiasm.

Fibers in the extrageniculate pathway continue in the brachium of the superior colliculus past the lateral geniculate nuclear to reach the pretectal area just rostral to the midbrain.

After synapsing, axons then continue bilaterally to the Edinger-Westphal nuclei, which contain preganglionic parasympathetic neurons.

Some of the crossing fibers travel in the posterior commissure. The Edinger-Westphal nuclei lie just dorsal and anterior to the oculomotor nuclei near the midline. Preganglionic parasympathetic fibers travel bilaterally from the Edinger-Westphal nuclei via the oculomotor nerves to reach the ciliary ganglia in the orbit.

From there, postganglionic parasympathetics continue to the pupillary constrictor muscles to cause the pupils to become smaller.

Note that a light shown in one eye causes a direct response in the same eye and a consensual response in the other eye b/c information crosses bilaterally at multiple levels.

Occurs when a visual object moves from far to near.

Three components:
1. Pupillary constriction
2. Accommodation of the lens ciliary muscle
3. Convergence of the eyes.

Activated by visual signals relayed to the visual cortex. From there, thru pathways still unknown, the pretectal nuclei are again activated, causing bilateral pupillary constriction mediated by the parasympathetic pathways.

Contraction of the ciliary muscle of the lens is parasympathetically mediated by the same pathway.

Note that the lens is normally under tension from the suspensory ligament. The ciliary muscle acts as a sphincter (like the pupillary constructor), so when it contracts it causes the suspensory ligament to relax, producing a rounder, more convex lens shape.

A descending sympathetic pathway from the hypothalamus travels in the lateral brainstem and cervical spinal cord to reach thoracic spinal cord levels T1 and T2.

This descending pathways activates preganglionic sympathetic neurons in the IML of the upper thoracic cord.

Axons of the preganglionic sympathetic neurons exit the spinal cord via ventral roots T1 and T2, and join the paravertebral sympathetic chain via white rami communicantes.

The axons synapse in the superior cervical ganglion. From there, postganglionic sympathetic fibers ascend thru the carotid plexus along the walls of the internal carotid artery, ultimately reaching the pupillary dilatory muscle.

Sympathetic pathway is also important in controlling the smooth muscle of the superior tarsal muscle which elevates the upper lid, causing a wide-eyed stare in conditions of increased sympathetic outflow.

These pathways also innervate the smooth muscle orbitalis, which prevents the eye from sinking back in the orbit, as well as the cutaneous arteries and sweat glands of the face and neck.

Pupillary asymmetry

1. Ptosis
2. Miosis
3. Anhidrosis

1. Lateral brainstem (infarct or hemorrhage)
2. Spinal cord trauma
3. First and second thoracic roots (pancoast's tumor or trauma)
4. Sympathetic chain trauma or tumor
5. Carotid plexus dissection
6. Cavernous sinus problems
7. Orbit infection or neoplasm

The sympathetics for sudomotor innervation diverge from the oculosympathetic pathway before the superior cervical ganglion.

Large bilateral lesions of the pons are sometimes associated with pontine pupils, in which both pupils are small but reactive to light.

This small pupillary size is probably caused by bilateral disruption fo the descending sympathetic pathways.

An afferent pupillary defect.

In this condition the direct response t light in the affected eye is decreased or absent, while the consensual response of the affected eye to light in the opposite eye is normal.

This defect is caused by decreased sensitivity of the affected eye to light, resulting from lesions of the optic nerve, retina, or eye.

A useful way to detect an afferent pupillary defect is with the swinging flashlight test. The flashlight is moved back and forth between the eyes every 2-3s.

The afferent pupillary defect becomes obvious when the flashlight is moved from the normal to the affected eye, and the affected pupil dilates in response to light.

*This abnormal dilation should be distinguished from hippus, which is a normal brief oscillation of the pupil size that sometimes occurs in response to light.

Opiates cause bilateral pinpoint pupils, and barbiturate overdose can also cause bilateral small pupils, mimicking pontine lesions.

Anticholinergic agents affecting muscarinic receptors, such as scopolamine or atropine, can cause dilated pupal.

1% pilocarpine eyedrops can be useful b/c they cause pupillary constriction in parasympathetic lesions but cannot overcome pharmacological muscarinic blockage.

A slight pupillary asymmetry of less than 0.6 mm is seen in 20% of the general population.

This can vary from one examination to the next. There are no association abnormal findings, such as dilation lag, changes in the asymmetry with lighting conditions, or eye movement abnormalities.

In light-near dissociation, the pupils constrict much less in response to light than to accommodation.

The mechanism for this disparity is not known for certain, and the mechanism may not be the same in different disorders.

A classic example of light-near dissociation associated w/neurosyphilis, in which, in addition to light-near dissociation, the pupils are small and irregular.

This disorder is characterized by degeneration of the ciliary ganglion or postganglionic parasympathetic neurons, resulting in a mid-dilated pupil that reacts poorly to light.

Some pupillary constriction can be elicited with the accommodation response, but the pupil then remains constricted and dilates very slowly. The cause is not known.

In this relatively rare condition, lesions of the midbrain can sometimes cause an unusual pupillary abnormality in which the pupil assumes an irregular, off-center shape.

Eye opening is performed by striated skeletal muscle of the levator palpebrae superioris together with Muller's smooth muscle in the upper lid. The frontalis muscle of the forehead (CN VII) performs an accessory role.

Eye closure is performed by the orbicularis oculi muscle (CN VII)

Drooping of the upper eyelid.

Can be seen in Horner's syndrome. Other causes of unilateral or bilateral ptosis include oculomotor nerve palsy affecting the levator palpebrae superior, myasthenia gravis, and redundant skin folds associated with aging.

Causes of bilateral ptosis or closed eyes without loss of consciousness include non-dominant parietal lobe lesions, dorsal lesions of the oculomotor nuclei affecting the central caudal nucleus, and voluntary eye closure associated with phototopia in migraine or meningeal irritation.

Careful exam of the lids using the irises as a reference point can usually resolve this dilemma; in ptosis the upper lid comes down farther over the iris in the affected eye, while in facial weakness the palpebral fissure is widened mainly b/c of sagging of the lower lid in the affected eye.

Consists of a collection of venous sinusoids located on either sides of the pituitary that receives venous blood from the eye and superficial cortex and ultimately drains via several pathways into the internal jugular vein.

It lies between the periosteal and dural layers of the dura mater.

It contains:
1. CN VI
2. CN III
3. CN IV
4. CN V1 (opthalmic division of trigeminal)
5. CN V2 (maxillary division of trigeminal)
6. Internal carotid a.

This is the region where nearly all nerves, arteries, and veins of the orbit converge before communicating with the intracranial cavity via the optic canal and superior orbital fissure.

Disrupts CN III, IV, an VI, causing total opthalmoplegia, usually accompanied by a fixed, dilated pupil.

Can also causes sensory loss due to involvement of CN V1 and V2.

Produces the same deficits as cavernous sinus syndrome, but they are more likely to involve CN II also, causing visual loss, and often are associated with proptosis, or bulging of the eye, due to mass effect in the orbit.

1. Metastatic tumores
2. Direct extension of nasopharyngeal tumors
3. Meningioma
4. Pituitary tumors
5. Aneurysms of the intracavernous carotid
6. Cavernous carotid arteriovenous fistula
7. Bacterial infection causing vacernous sinus thrombosis
8. Idiopathic granulomatous disease (Tolosa-Hunt syndrome)
9. Fungal infections such as aspergillosis or murcomycosis.

1. Metastatic tumors
2. Orbital cellulitis (bacterial infection)
3. Idiopathic granulomatous disease (orbital myositis or pseudotumor)
4. Fungal infections such as aspergillosis

These are rapid eye movements reaching velocities of up to 700 degrees per second. They function to bring targets of interest into the field of view.

Vision is transiently suppressed during saccadic eye movements.

Saccades are the only type of eye movements that can easily be performed voluntarily, although they can be elicited by reflexes as well.

These eye movements are not under voluntary control; they reach velocities of only 100 degrees per second.

They allow stable viewing of moving objects.

These eye movements maintain fused fixation by both eyes as target move toward or away from the viewer. The velocity is about 20 degrees per second.

These eye movements include optokinetic nystagmus and the vestibulo-ocular reflex.

It is a rhythmic form of reflex eye movements composed of slow eye movements in one direction interrupted repeatedly by fast saccade like eye movements in the opposite direction

1. Medial longitudinal fasciculus (MLF)
2. Abducens nucleus
3. Paramedian pontine reticular formation (PPRF)

This interconnects the oculomotor, trochlear, abducens, and vestibular nuclei.

Through connections in the MLF, eye movements are normally yoked together, resulting in conjugate gaze in all directions. For example, during horizontal eye movements the actions of the aducens and oculomotor nuclei are coordinated thru connections in the MLF.

Through this circuit in the MLF, the abducens nucleus does more than just control abduction of the ipsilateral eye. In reality, the abducens nucleus is a horizontal gaze center, controlling horizontal movements of both eyes in the direction ipsilateral to the side of the nucleus.

In the pontine tegmentum near the abducens nucleus is an additional important horizontal gaze center called the PPRF that provides inputs from the cortex and other pathways to the abducens nucleus, resulting in lateral horizontal gaze.

Lesions of the abducens nerve cause impaired abduction of the ipsilateral eye.

Lesions of the abducens nucleus produces an ipsilateral lateral gaze palsy involving both eyes b/c of the connections through the MLF.

Similarly, lesions of the PPRF cause an ipsilateral lateral gaze palsy.

Lesions of the MLF interrupt the input to the medial rectus. Therefore the eye ipsialteral to the lesion does not adduct fully on attemted horizontal gaze.

In addition, for uncertain reasons there is also nystagmus of the opposite eye, possibly b/c of mechanisms trying to bring the eyes back into alignment.

This is the classic neurologic syndrome produced by an MLF lesion. In an INO, eye adduction on the affected side is impaired with horizontal gaze but is often spared during convergence b/c the inputs to the oculomotor nucleus mediating convergence arise from the pretectal region and hence do not travel in the caudal MLF.

Include MS plaques, pontine infarcts, or neoplasms involving the MLF.

A subtle INO can sometimes be detected only by testing of horizontal saccades in both directions and observation of a slight lag in the adduction of the eye on the affected side.

There is a combination of an ipsilateral INO and an ipsilateral lateral gaze palsy.

Results in "one-and-a-half syndrome"

The ipsilateral eye cannot move at all horizontally, and the contralateral eye loses half of its movements, preserving only its ability to abduct, resulting in the quaint name "one-and-a-half syndrome"

The rostral midbrain reticular formation and pretectal area.

The ventral portion of this region is thought to mediate downgaze, while the more dorsal region mediates upgaze.

An important nucleus that is thought to mediate downages is the rostral interstitial nucleus of ht eMLF.

Convergence of the eyes is produced by the medial recti.

Divergence is produced by the lateral recti.

Vergence movements are under the control of descending inputs from the visual pathways in the occipital and parietal cortex and constitute part of the accommodation response.

1. Impairment of vertical gaze, especially upgaze. This may be due to compression of the dorsal part of the vertical gaze center.

2. Large, irregular pupils that do not react to light but sometimes may react to near-far accommodation.

3. Eyelid abnormalities ranging from bilateral lid retraction or "tucking" to bilateral ptosis.

4. Impaired convergence, and sometimes convergence-retraction nostagmus, especially on attempted upgaze (the eyes rhythmically converge and retract in the orbits).

The most common causes are pineal region tumors and hydrocephalus.

Hydrocephalus can cause dilation of the suprapineal recess of the third ventricle which pushes downward onto the collicular plate of the mibrain.

Thus, hydrocephalus, especially in children, can produce the bilateral setting-sun sign, in which the eyes are deviated inward b/c of bilateral sixth nerve palsies and downward b/c of a Parinaud's syndrome.

Descending cortical pathways travel either directly to the brainstem centers for horizontal, vertical, or convergence eye movements or via relays in the midbrian superior colliculi.

The best-known cortical area that controls eye movements consists of the frontal eye fields.

The frontal eye fields generate saccades in the contralateral direction via connections to the contralateral PPRF.

More posterior cortical regions of the parieto-occipito-temporal cortex are primarly responsible for smooth pursuit movements in the ipsilateral direction, via connections with the vestibular nuclei, cerebellum, and PPRF.

The parieto-occipito-temporal cortex may make some contribution to contralateral eye movements as well.

The basal ganglia also play a role in modulatory control of eye movements, and characteristic disorders of eye movements can be seen in basal ganglia dysfunction.

Normally impair eye movements in the contralateral direction, often resulting in a gaze preference toward the side of the lesion.

This gaze preference is typically accompanied by weakness contralateral to the cortical lesion (if the corticospinal pathways are involved), so that the eyes look away from the side of the weakness.

Certain situations can cause the eyes to look toward the side of the weakness. This condition is called wrong-way eyes.

Causes include seizure activity in the cortex, which can drive the eyes in the contralateral direction b/c of activatino of the frontal eye fields, while also causes abnormal or decreased movements of the contralateral side of the body b/c of involvement of motor association cortex and other structures.

Large lesions such as thalamic hemorrhage can disrupt the corticospinal pathways of the internal capsule, casing contralateral weakness, yet may also cause the eyes to deviate toward the side of the weakness.

Lesions of the pontine basis and tegmentum can cause wrong-way eyes b/c disruption of the corticospinal fibers causes contralateral hemiplegia, while involvement of the abducens nucleus or PPRF causes ipsilateral gaze weakness.

The examiner can elicit OKN in the horizontal direction by moving a thick ribbon with vertical stripes horizontally in front of the eyes.

The eyes alternate between smooth pursuit movements in the direction of stripe movement and backup saccades opposite the direction of stripe movement in an attempt to stabilize the image.

OKN is sometimes called train nystagmus b/c it can be observed in the eyes of fellow passengers as they watch the passing visual scene thru an open window.

The slow phase, or smooth pursuit phase of OKN, is mediated by the ipsilateral posterior cortex, with connections to the vestibular nuclei and flocculonodular lobe of the cerebellum projecting to the PPRF and abducens nuclei.

The fast phase, or saccadic phage of OKN is mediated by the frontal eye fields projecting ultimately to the contralateral PPRF.

Therefore, lesions of the frontal cortex or anywhere in the saccadic pathways disrupt the fast phases of OKN, while the slow phases are disrupted by lesions in the smooth pursuit pathways.

VOR stabilizes the eyes on the visual image during head and body movements.

Inputs from the vestibular nuclei, especially the medial vestibular nuclei, travel in the MLF to control the extraocular nuclei.

The VOR can be tested with the oculocephalic maneuver or with cold water calorics.

Compatible with an oculomotor nerve palsy in the left oculomotor nerve commonly caused by aneurysm where the PComm branches off from the internal carotid.

This patient has dysfunction of the left lateral rectus muscles causing dysconjugate horizontal gaze, and diplopia.

Most likely Dx is an isolated left abducens nerve palsy.

These findings are compatible with a rigth trochlear palsy.

Most likely cause is an idiopathic neuropathy of presumed microvascular origin.

Possible cause is from a lesion that restricts movements of the left lateral rectus muscle due to orbital trauma.

This patient has dysfunction of the left CN III, IV, VI, and V1, constituting a left cavernous sinus syndrome.

Dx: Horner's syndrome due to lesion in left sympathetic chain.

This patient has a combo of a left horizontal gaze palsy and right hemisparesis constituting so called wrong way eyes.

Most likely Dx is an infarct in the left pons involving the left corticospinal and corticobulbar fibers as well as the left abducens nucleus (or PPRF).

Could also be due to seizures in left hemisphere.

These findings constitute a left INO localized to the left MLF.

These finding constitute a left INO plus a left horizontal gaze palsy, also called one and a half syndrome.

This patient has a classic Parinaud's syndrome due to compression of or lesions in the dorsal midbrain.

Demyelinating diseases of the CNS are acquired conditions characterized by preferential damage to myelin, with relative preservation of axons.

The clinical deficits are due to the effect of myelin loss on the transmission of electrical impulses along axons.

MS is an autoimmune demyelinating disorder characterized by distinct episodes of neurological deficits separated in time, attributable to white matter lesions that are separated in space.

Affects 1/1,000 persons in most of US and Europe. Women are affected 2x more than men.

The clinical course of the illness evlolves as relapsing and remitting episodes of neurologic deficit during variable interval of time (wks to mos to yrs) followed by gradual, partial recovery of neurologic function. The frequency of relapses tends to decrease during the course of time, but there is a steady neurologic deterioration in most patients.

The lesions of MS are caused by a cellular immune response that is inappropriately directed against the components of the myelin sheath.

The likely hood of developing this autoimmune process is influenced by genetic and environmental factors.

Risk is 15x higher when the disease is present in a first degree relative and higher for twins. Genetic linkage of MS susceptibility to the DR2 extended haplotype of the MHC is also well established.

The molecular basis for influence of this particular haplotype on the risk of developing MS is unknown, other genetic local are involved as well.

The available evidence indicates that the disease is initiated by CD4+ TH1 cells that react against self myelin antigens and secrete cytokines, such as IFN-γ, that activate macrophages.

The demyelination is caused by these activated macrophages and their injurious products.

The infiltrate in plaques and surrounding regions of the brain consists of T cells (mainly CD4+, some CD8+), and macrophages.

Antibodies are also freq present. Therapies are being developed that modulate or inhibit TH1 responses and block the recruitment of T cells into the brain.

Since MS is a white matter disease and gray matter covers much of the surface of hemispheres, macroscopic exam of the outer cortex is unremarkable.

Evidence of disease may be found on the surface of the brainstem or along the spinal cord, where myelinated fiber tracts course superficially; here lesions appear as multiple, well-circumscribed, somewhat depressed, glassy, gray-tan, irregularly shaped plaques, both on external exam and on section.

In the fresh state, these have firmer consistency than the surrounding white matter (sclerosis).

Lesions (plaques) are sharply defined areas of gray discoloration of white matter occurring esp around the ventricles but potentially located anywhere in the CNS.

Active plaques show myelin breakdown, lipi-laden macrophages, and relative axonal preservation. Lymphocytes and mononuclear cells are prominent at the edges of plaques and around venules in and around plaques.

Inactive plaques lack the inflammatory cell infiltrate and show gliosis; most axons within the lesion persist but remain unmyelinated.

Plaques can be found throughout the white matter of the neuraxis; they may also extend into the gray matter structures, as these have myelinated fibers running through them.

Plaques commonly occur beside the lateral ventricles and may be demonstrated to follow the course of paraventricular veins when the surface of the ventricle is inspected en face. They are also frequent in the optic nerves and chiasm, brain stem ascending and descending fiber tracts, cerebellum, and spinal cord.

Although MS lesions can occur anywhere in the CNS and, as a consequence, may induce a wide range of manifestations, certain patterns of neurologic symptoms are commonly observed.

Unilateral visual impairment during the course of a few days, due to involvement of the optic nerve (optic neuritis) is a frequent initial manifestation of MS.

Involvement of the brainstem produces cranial nerve signs, ataxia, nystagmus, and internuclear ophthalmoplegia from interruption of the fibers of the medial longitudinal fasciculus (MLF).

Spinal cord lesions give rise to motor and sensory impairment of trunk and limbs, spasticity, and difficulties w/the voluntary control of bladder function.

Exam of the CSF in MS patients shows a mildly elevated protein level, and in one third of cases, there is moderate pleocytosis. The proportion of gamma globulin in increased, and most MS patients show oligoclonal bands.

This increase in CSF immunoglobulin is the result of proliferation of B cells within the nervous system; the target epitopes of these antibodies are wildly variable.

Some individuals, especially Asians, develop a demyelinating disease similar to MS with presenting symptoms of bilateral optic neuritis and prominent spinal cord involvement.

This disease is referred to as neuromyelitis optica or Devic disease.

It may be rapidly and relentlessly progressive, following a relapsing-remitting course, or manifest as a single episode without subsequent relapses.

The lesions in Devic disease are similar in histologic appearance to MS, although they are considerably more destructive, and gray matter involvement of the spinal cord can be striking.

Tends to occur in young individuals and is characterized clinically by a fulminant course during a period of several months.

On pathological examination, the plaques are large and numerous, and there is widespread destruction of myelin with some axonal loss.

This is a monophasic demyelinating disease that follow either a viral infection or, rarely, a viral immunization. Symptoms typically develop a week or two after the antecedent infection and include evidence of diffuse brain involvement with headache, lethargy, and coma rather than focal findings, as seen in MS.

Symptoms progress rapidly, with a fatal outcome in as many as 20% of cases; in the remaining patients there is complete recovery.

Macroscopic exam of the brain shows only grayish discoloration around white matter vessels. On microscopic exam, myelin loss with relative preservation of axons can be found throughout the white matter. In the early stages of the disease, polymorphonuclear leukocytes can be found within the lesions; later, mononuclear infiltrates predominate.

The breakdown of myelin is associated w/the accumulation of lipid laden macrophages.

This is a fulminant syndrome of CNS demyelination, typically affecting young adults and children.

The illness is almost invariably preceded by a recent episode of upper respiratory infection.

Sometimes, it is due to Mycoplasma pneumoniae, but often it is of indeterminate cause.

The disease is fatal in many patients, but some have survived with minimal residual symptoms.

Shows histologic similarities with ADEM, including perivenular distribution of demyelination and widespread dissemination throughout the CNS.

However, the lesions are much more devastating than those of ADEM and include destruction of small blood vessels, disseminated necrosis of white and gray matter with acute hemorrhage, fibrin deposition, abundant neutrophils, and scattered lymphocytes recognizable in less severely damaged areas and in foci of demyelination.

ADEM may represent an acute autoimmune reaction to myelin and ANHE may represent a hyperacute variant, although no inciting antigens have been identified.

Characterized by loss of myelin (with relative preservation of axons and neuronal cell bodies) in a roughly symmetric pattern involving the basis pontis and portions of the pontine tegmentum but sparing the periventricular and subpial regions.

Lesions may be found more rostrally; it is extremely rare for the process to extend below the pontomedulalry junction.

Extrapontine lesions occur in the supratentorial compartment, with similar appearance an apparent etiology.

The condition is believed to be caused by rapid correction of hyponatremia; however, alternative pathogenetic hypotheses attribute the disorder to extreme serum hyperosmolarity or other metabolic imbalance.

It is taht of a rapidly evolving quadriplegia; radiologic imaging studies localize the lesion to the basis pontis.

It occurs in a variety of clinical settings, including alcoholism, severe electrolyte or osmolar imbalance, and orthotopic liver transplantation.

This is a rare disorder of myelin characterized by relatively symmetric damage to the myelin of central fibers of the corpus callosum and anterior commissure.

Autoimmune disease can be caused by antibodies that perturb a normal physiological function or by inflammatory T cells that damage healthy cells or tissue at a rate that is beyond the capacity of the body to repair.

They are caused by unwanted adaptive immune responses; they represent failures of the mechanisms that maintain self tolerance - the prevention of attack on the body's own cells and tissues - in the populations of circulating B and T cells.

They vary widely in the tissue types they attack and the symptoms they cause. Some focus on a particular organ or cell type, other act systemically.

For most autoimmune disease the incidence differs between females and males, with females being more commonly affected.

A defining characteristic of autoimmune disease is the presence of antibodies and T cells specific for antigens expressed by the targeted tissue.

The antigens expressed by the targeted tissue are called autoantigens and are a subset of the self-antigens.

The effects of adaptive immunity that recognize them are known as autoantibodies and autoimmune T cells.

Type I
-caused by IgE and not involved in autoimmune reactions

Type II
-caused by antibodies directed against components of cell surfaces or the ECM

Type III
- caused by the formation of soluble immune complexes that are deposited in tissues

Type IV
-caused by effector T cells

A type II hypersensitivity reaction directed at the cells of the blood.

IgG and IgM antibodies bind to components of the erythrocyte surface, where they activate complement by the classical pathway, triggering the destruction of red cells.

Complete activation of the classical pathway leads to formation of the membrane-attack complex and hemolysis of red cells.

Alternatively, erythrocytes coated w/antibody or C3b are cleared from the circulation, principally by Fc and complement receptors on phagocytes in the spleen.

End result is anemia.

WBCs can also be a target for autoantibodies and complement activation.

B/c nucleated cells are less susceptible than erythrocytes to complement mediated lysis, the major effect of complement activation is to facilitate phagocyte-mediated clearance of WBCs in the spleen.

Patients then develop neutropenia. Treatment is splenectomy.

Type II hypersensitivity

IgG is formed against the α₃ chain of type IV collagen, the collagen foudn in basement membranes throughout the body.

The antibodies deposit along the basement membranes of renal glomeruli and renal tubules, eliciting an inflammatory response in the renal tissue. These basement membranes are an essential part of the blood filtering mechanism of the kidney, as IgG and inflammatory cells accumulate, kidney function becomes progressively impaired, leading to kidney failure and death if not treated.

Treatment involves plasma exchange to remove existing antibodies and immunosuppressive drugs to prevent the formation of new ones.

Can also be a consequence of autoimmune diseases that produce soluble immune complexes, as in type III hypersensitivity reactions.

1. The function of an endocrine gland, the synthesis and secretion of a particular hormone, involves tissue-specific proteins not expressed in other cells or tissues.

2. B/c they secrete their hormones into the blood, endocrine cells are well vascularized, which facilitates interactions w/the cells and molecules of the immune system.

For these reasons, such diseases are called organ-specific autoimmune diseases.

The proteins thyroglobulin, thyroid peroxidase, TSH receptor and the thyroid iodide transporter are uniquely expressed in thyroid cells.

Immune responses to all these autoantigens have been detected in autoimmune thyroid disease.

In Graves' disease, the autoimmune resposne is focused on antibody production and the symptoms are caused by antibodies that bind to the TSH receptor.

By mimicking the natural ligand, the bound antibodies cause a chronic overproduction of thyroid hormones that is independent of regulation by TSH and insensitive to the metabolic needs of the body.

This hyperthyroid condition causes heat intolerance, nervousness, irritability, warm moist skin, weight loos, and enlargement of the thyroid.

Other aspects of the disease are outwardly bulging eyes and a characteristic stare, symptomes caused by the binding of autoantibodies that react w/the muscles of the eye.

The autoimmune response is biased towards a CD4 TH2 response. Treatment is thyroidectomy or destruction by uptake of a radioisotope followed by daily doses of thyroid hormone.

The thyroid loses the capacity to make thyroid hormones.

Hashimoto's disease seems to involve a CD4 TH1 cell response, and both antibodies and effector T cells specific for thyroid antigens are produced.

Lymphocytes infiltrate the thyroid, causing a progressive destruction of the normal thyroid tissue. The formation of organized lymphoid tissue within the thyroid, including germinal centers, gives the impression that they thyroid is being converted into a secondary lymphoid tissue.

Patient become hypothyroid, and eventually need to take synthetic thyroid hormones orally on a daily basis.

The transfer of autoantibody from the patient to another human or to an animal will induce disease.

T-cell mediated autoimmune diseases cannot be passed from mother to fetus and they cannot be tranferred to experimental animals.

Such experiments fail to work b/c human T cells cannot recognize antigens presented by the MHC molecules of most other species.

Type IV hypersensitivity reaction.

In patients w/IDDM, antibody and T-cell responses are made against insulin, glutamic acid decarboxylase, and other specialized proteins of the pancreatic β cell.

CD8 T cells specific for some peptide antigens unique to β cells are believed to mediate β-cell destruction, gradually decreasing the number of insulin secreting cells.

Individual islets become successively infiltrated w/lymphocytes, a process called insulitis.

The usual treatment for patients with IDDM is daily injection with insulin purified from the pancreas of pigs or cattle. Because of amino-acid sequence differences between human insulin and animal insulins, some patients develop an immune reponse to animal insulin.

The antibodies they make against insulin can have two effects: they reduce the activity of the insulin, and they form soluble immune complexes that can lead to further tissue damage.

Recombinant human insulin produced in the laboratory from the cloned insulin gene is prescribed to patients who make antibodies against animal insulins.

Type III hypersensitivity reaction

In this disease the autoimmune response is directed at autoantigens present in almost every cell of the body.

Characteristics of SLE are circulating IgG antibodies specific for constituents of cell surfaces, cytoplasm, and nucleus, including nucleic acids and nucleoprotein particles.

The binding of autoantibodies against cell surface components inititates inflammatory reactions that cause cell and tissue destruction. In turn, these process release soluble cellular antigens that form soluble immune complexes.

Common sites of disease in SLE are the joints, where the deposition of immune complexes causes inflammation and arthritis.

Over 90% of patients with SLE suffer from arthritis and it is often the first symptom to be noticed. SLE is one of a number of rheumatic diseases, almost all of which are autoimmune in nature.

Type IV hypersensitivity reaction.

In 80% of patients with RA is the stimulation of B cells that make IgM, IgG, and IgA antibodies specific for the Fc region of human IgG. Rheumatoid factor is the name given to their anti-Ig autoantibodies.

Treatment is with anti-inflammatory and immunosuppressive drugs. Treatment with antibody against tumor necrosis factor-α (TNF-α) is also used to alleviate the symptoms.

Type IV hypersensitivity reaction

Activated TH1 CD4 cells and the interferon-γ (IFN-γ) they secrete are the effectors implicated in multiple sclerosis. These cells are enriched in the blood and cerebrospinal fluid.

Activated macrophages are present in sclerotic plaques; these
release proteases and cytokines, which are the direct cause of demyelination.

The effect of IFN-γ was most clearly demonstrated by a clinical trial of this cytokine as a possible treatment; tragically, the disease worsened in the patients treated with IFN-γ.

In 90% of patients the sclerotic plaques contain plasma cells that secrete oligoclonal IgG into the cerebrospinal fluid.

The autoantigens in multiple sclerosis are thought to be structural proteins of myelin, such as myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein.

Regular subcutaneous injection of IFN-β1 reduces the incidence of disease attacks and the appearance of plaques. High doses of immunosuppressive drugs are used to reduce the severity of disease episodes.

This is an autoimmune disease in which signaling from nerve to muscle across the NMJ is impaired. Autoantibodies bind to the ACh receptors on muscle cells, inducing their endocytosis and intracellular degradation in lysosome. The loss of cell surface ACh receptors makes the muscles less sensitive to neuronal stimulation.

Consequently, patients suffer from progressive muscle weakening as levels of autoantibody rise.

One treatment for myasthenia gravis is the drug pyridostigmine, an inhibitor of the enzyme cholinesterase, which degrades acetylcholine.

By preventing acetylcholine degradation, pyridostigmine increases the capacity of acetylcholine to compete with the autoantibodies for the receptors.

A second treatment for myasthenia gravis is the immunosuppressive drug azathioprine, which inhibits the production of autoantibodies.