Neeuro-opthalmology

 

Neuroopthalmology

Neuroopthalmology is the field of specialization dealing with the portions of nervous system related to the eye.

Neuroopthalmologist the specialist who deals in this specialization is known as neuroopthalmologist

QUALIFICATIONS

A neuroopthalmologist must have the following education

Four years at college or university to earn BA or BS degree

Four years of undergraduate medical education at U.S. medical schools

After completing their medical school, students earn their doctor of medicine degree, MDs

Residency program of 3-7 years

Fellowship for 1-3 years

Major diseases treated in this specialty

Migraine

Myasthenia gravis

Intracranial aneurysms

MIGRAINE

Migraine is an often-familial disease characterised by recurrent attacks of headache widely variable in intensity, duration and frequency

SIGNS AND SYMPTOMS

COMMON MIGRAINE

Changes in mood, frequent yawning, poor concentration, headache, attack lasts from hours to a day or more, patient usually becomes photophobic or homophobic.

CLASSICAL MIGRAINE

Visual auras lasting for 20 minutes, bright dark spots, zigzags, heat haze distortions, jigsaw puzzle effects, and tunnel vision

CLUSTER HEADACHE

Unilateral, occulotemporal headache, beginning abruptly lasting for 10mins to 2 hours. Once this cluster is over, there may be a long headache free interval of several years.lacrymation, rhinnorehea, and conjuctival infection. May be the autonomic phenomena.

DIAGNOSIS

The patient may report loss of vision in the eye ipsilateral to the hemianopia.

RISK FACTORS

SEX most common in females

AGE middle-aged patients are more prone

DIET  alcohol, caffine, chocolate, and nuts, home made yeast. Breads etc.

HORMONES menses, ovulation, menopause, pregnancy etc.

STREESS marriage, divorce, birth, death etc.

CHANGE IN ROUTINE waather, travel, sleeping pattern etc.

PATHOPHYSIOLOGY of headache

Both vascular and neuronal events occur in the pain of migraine.

The locus circulars in the pons are the origin of nor adrenergic pain control system.

Ascending fibers innervate the brains microcirculation and also project to the cerebral cortex.

Descending fibers go to the spinal cord the serotogenic system from mid brain raphe is also involved.

This system affects both intracranial and extra cranial blood vessels and has connections to thalamus, hypothalamus and the cerebral cortex.

The descending serotogenic system originates in the midbrain periaquaductal gray matter, runs to raphe Magnus in medulla and terminates in the spinal cord.

These fibers are involved in pain regulation.

POTENTIAL TEREATMENT

Careful history and physical examination.

Patient education and counseling.

General measures include elimination of conditions and agents that may precipitate a migraine attack.

Pharmacotherapy

      Prophylactic migraine therapy

Beta-blockers propranolol, atenolol, timolol

Calcium channel blockers verapamil, diltiazem, nifedipine

Antidepressants amitriptyline, doxepin, sertraline

Miscellaneous valproate, phenytioin

      Symptomatic migraine therapy

Simple analgesics aspirin, acetaminophen, caffeine

Combination analgesics acetaminophen, isometheptene, dichlorophenazone, aspirin/caffine/butalbital

NSAIDS ibuprofen naproxen diclofenac flurbiprofen

Ergot alkaloids  ergotamine tartarate dihydroergotamine

Sever persistent pain chlorpromazine haloperidol thiothixine

Adjunct therapy antiemetics antihistaminics benzodiazepines

Nonpharmacologic treatment includes physical therapy, heat, ice, exercise etc.

MYASTHENIA GRAVIS 

It is an uncommon autoimmune disorder, characterized by weakness and fatigability of voluntary musculature.

SIGNS AND SYMPTOMS

Ocular features

Ptosis

It is insidious, bilateral and frequently asymmetrical. If one eyelid is elevated manually the patient looks up, other eye shows fine oscillatory movements.

Cogan twitch sign brief upshot of the eyelid as eyes saccade from depression to primary position

Diplopia

It is a frequently ipsilateral, although any of all of extraocular muscles may be affected

Nystagmoid movements

They may be present on extremes of gaze

General features

      Limb weakness, abnormal fatigue on exercise

      Lack of _expression, rarely difficulty with breathing may occur

Bulbar features

Dysphagia, dysarthria

DIAGNOSTIC TESTS

1 positive edrophonium test

2 raised serum acetyl choline receptor antibiotic levels

3 thoracic CT scan or MRI

4electromyograrphy

RISK FACTORS

AGE most common in the third decade

SEX affects females twice as compared to females.

PATHOPHYSIOLOGY 

In 80-9% cases,myasthenia gravis is caused by anti-acetylcholine receptor antibody but the level of antibody positivity in patients with ocular myasthenia gravis is much lower than in patients with systemic myasthenia gravis

TREATMENT

Treatment of ocular disease

      Course of oral steroids(40-60mg daily for a period of 3-4 months)

      Majority of patients may resond to azathioprine in long term

PROGNOSIS

Poor

Relapse rate high

Only a smallpercentage of patients with urely ocular disease require thymectomy to bring their disease under control.

BELL’S PALSY

Signs and symptoms



Although it is tempting to label all acute facial palsies as “ idiopathic” (i.e. Bell’s palsy) 10% of the patients referred with a diagnosis of Bell’s palsy were found to have a treatable progressive, or life – threatening lesion Bell’s palsy is a diagnosis of exclusion. reserved for cases in witch all other causes of acute acquired, isolated peripheral facial paralysis have been considered and invest – gated if necessary. Although Bell’s palsy is a term resaved to designate an acute peripheral facial palsy of unknown cause accumulating evidence supports a viral inflammatory – immune mechanism. In about 60% of cases, Bell’s palsy is associated with viral prodrome. The disorder is self limiting is nonprogressve, is not life threatening, and spontaneously recovers; at this time it can be neither prevented nor cured. Subjective complaints include pain around the ear (50%) facial numbness (40%) changes in taste (50%) and numbness of the tongue (20%)16 A family history of facial palsies is noted in 14% of patients, and the syndrome is recurrent in 12%. Of those with a history of recurrence the same side is involved in 36%. Disturbances of the stapes reflex ( dysacusis; failure to dampen the vibrating ear ossicles, as determined by middle ear function studies) loss of taste anterior two thirds of the tongue and decreased sublingual and submandibular salivery secretion are most suggestive of a lesion in the tympanomastiod protion of the facial never.16. The onset of facial palsy is not in itself diagnostic. Tumors, like Bell’s palsy may present with incomplete complete, sudden, slowly progressive or recurrent ipsilateral peripheral facial palsy. However, when a facial nerve palsy progresses for more then 3 weeks a tumor must be excluded. In some cases of otherwise uncomplicated Bell’s palsy examination of the spinal fluid reveals a pleocytosis and an increase in protein without a microorganism being disclosed.23 Bell’s palsy appears to have a higher incidence during reganacy. Third trimester of pregnancy and there was no apparent relationship between toxemia. Prim parity, and hyper-tension. Finally there appears to be a genetic predisposition to Bell’s palsy. When one considers the degree of palsy and uses electromyography dada. The prognosis for recovery of facial function can be predicted with a high degree of accuracy. Ninety percent of patients will have a satisfactory recovery if the palsy is incomplete and the response to evoked electromyography ( performed with supra maximal stimuation of the facial nerve at the stylomas - toid foramen ) remains greater then 10%of normal be yond the first 14 days after onset. Patients who do not fulfill these criteria nonetheless have at least a 50% change of satisfactory recovery 29 ( i.e. complete or near complete return of facial function ).

Pathophysiology

A variety of viral agents have been associated with idiopathic facial palsy, but the herpes group of viruses has been the one most often implicated.31 The diagnostic evaluation of patients with acute facial palsy requires consideration of entitles such as Lyme disease, HIV infection , sarcoid , herpes infection, syphilis and a variety of meningeal processes. Magnetic resonance imaging (MRI) is not routinely performed in the evaluation of patients with Bell’s palsy. However, nonspecific gadolinium enhancement of the facial nerve is

Often observed. The severity of the facial palsy has no relationship to the findings on MRI, and the unaffected facial nerve may also show pathologic enhancement.34

Treatment



Treatment for Bell's palsy is supportive, involving heat, massage, and facial exercises. Decompressive surgery has not been shown to alter the natural history of Bell's palsy, and the use of steroids is controversial. For instance, there is no large, well-controlled study that supports the efficacy of steroids."'536 At present, the decision regarding the use of steroids should be individualized. Considerations should include the patient's age, the patient's general medical condition, the duration and the completeness of the palsy, and the presence of pain. We do not use corticosteroids if it is possible that the facial palsy is caused by Lyme disease, because their administration may render this condition refractory to future antibiotic treatment. Although data is limited, the routine use of acyclovir in the treatment of Bell's palsy is, becoming more widely accepted. A recent small double blind study of Bell's palsy supports the combination of acyclovir and prednisone over prednisone alone.36" Further study is necessary to determine whether acyclovir should be used alone in Bell's palsy-

INFECTIOUS AND IMMUNE-MEDIATED NEUROPATHIES

Herpes Zoster Cephalicus (Ramsay Hunt Syndrome)

Hunt first described the syndrome of herpes zoster' cephalicus, which is characterized by a viral prodrome followed by severe pain in and around the ear, with > asides involving the external canal and pinna.3738 Vesiculation may involve the ear, face. neck, tongue, larynx, or buccal mucosa. The distribution of the vesicles depends on which sensory fibers are infected. Any of the nerve branches that communicate with the facial nerve may be involved, including cranial nerves V, VIII, IX, and X. and cervical nerves II through IV In the mildest form. Neurologist signs are absent, whereas in severe cases there may be accompanying sensor neural hearing loss.disturbed vestibular function, and even viral encephalitis. Herpes zoster cephalic us is characterized by vesicles, a high incidence of eighth cranial nerve involvement, post herpetic pain and a poorer prognosis for recovery of the facial palsy. The presence of hearing loss in a patient with suspected idiopathic facial palsy should strongly suggest varicella zoster virus infection.

The natural history of herpes zoster differs from that of Bell's palsy in several ways, perhaps reflecting the difference in behavior between herpes simplex type I and the varicella-zoster viruses, cell's palsy recurs in some 12% of cases, but herpes zoster cephialicus rarely recurs. In addition, the acute phase of the infection, as measured by electrical response and progression of facial weakness, peaks at 5 to 10 days with Bell's palsy, hut at 10 to 14 days with herpes /oster ceplialicus. Lastly. S4% of persons suffering from Bell's palsy have a satisfactory recovery of facial function, in contrast to 60% of those with herpes /osier cephalicus.

Treatment of herpes zoster is similar to that of Bell's palsy. But with the addition of therapeutics to control pain and vesicular eruption. Often, narcotics arc required. Advances in antiviral therapy provide further avenues of treatment Small studies have supported the efficacy of acyclovir in the treatment of herpes /oster cephalic us, hut its role has not been firmly established.4"'41

 Nystagmus in Infancy

There are several of begins nystagmus usually seen in infancy. Congenital usually common infantile nystagmus. Other is latent / manifest latent nystagmus (LMLM) and the pendular nystagmus of spasmus nutans. 

Congenital

Congenital nystagmus is usually present at birth or noted in early infancy at the time of development of visual fixation, and it persists throughout life. Rarely, CN becomes manifest later in life,<so the term congenital should be thought of as a congenital predisposition for this particular type of ocular motor instability rather than taken literally. This form of nystagmus may accompany primary visual defects, which has led to the assumption that the nystagmus is secondary to poor vision, and that both "sensory defect" and "motor defect" types of CN exist. In fact, recordings have shown that all CN is the same with regard to waveforms and underlying mechanism, regardless of the coincidental existence of a sensory deficit. CN is the direct result of an ocular motor control instability that may develop with or without an accompanying sensory deficit. Thus, for those cases in which a sensory deficit exists, it can only be a subordinate factor in the development of CN, perhaps interfering with the normal calibration of a key ocular motor subsystem and thereby precipitating its instability. The common association of "pendular" CN with a sensory defect and the "jerk" form with a primary motor abnormality is both simplistic and erroneous.

 The relationship of the visual detect to the nystagmus possibly represents simple genetic association. Although the visual problem may not be causal, it can contribute to the intensity of the nystagmus. CN represents a high-gain instability in a SEM'subsystem,8 and fixation attempt (the effort to see) is its main driving force. Poor vision will increase fixation effort and in- / crease the intensity of the nystagmus. Moreover, a sub clinical motor instability may become manifest by this exaggerated visual effort. Although the exact location of the source of the instability present in CN is unknown. we hypothesize that CN is due to a gain/delay problem in an internal (brain stem) feedback loop in the pursuit subsystem.8 The much greater incidence of horizontal CN, compared with vertical or diagonal CN. Probably reflects inherent differences in the stability of the respective pursuit subsystems (i.e., the horizontal is more unstable than the vertical. The Common integrator is not the site of the CN instability.9 several models have been proposed that attempt to explain the genesis of; CN.10'12 While each can generate some CN characteristics, they exhibit behaviors inconsistent with data from individuals with CN. Because CN appears to be activated and intensified by fixation attempt, the deficit may also be linked to the fixation subsystem. The co-existence of a high-frequency \ pendular oscillation with a low-frequency jerk CN (causing a dual-jerk waveform) in some subjects, and with LMLN in 'others, suggests that the high-frequency pendular oscillation is due to an instability at a different site. It has also been suggested that CN is caused by oscillations at two frequencies whose interactions may produce some of the known CN waveforms.13

Distinguishing the lower frequency pendular nystagmus from jerk nystagmus may be difficult clinically, particularly in CN. Certain forms of jerk nystagmus are invariably mislabed as pendular, or the direction is misidentified. Even with oculographic recordings, the direction of the fast phase may be misinterpreted unless velocity tracings are obtained.14 In the absence of oculography, clinicians should describe the nystagmus care-

Congenital nystagmus usually damps significantly with convergence. Although the exact mechanism responsible for this damping in unknown, we have long felt that it might result from an effective increase in the stiffness of the ocular motor plant brought about by the increased innervations to the antagonist medial recti. Because convergence results in a change in the muscle pulley system, 16 that may be the mechanism by which the stiffness is increased. The observations of convergence-induced damping of other types of nystagmus support this "peripheral" mechanism in preference to one relaying on an inherent property of CN. As previously mentioned, the intensity of CN is related to the fixation attempt, which probably explains why it sometimes persists with eyes open in darkness (when the subject will probably attempt to "see") and damps behind closed lids (when the subject will, unless instructed to the contrary, reduce any attempt to "see'').14 The denning criterion is fixation attempt, not retinal illumination or lid position. Therefore, reports of the presence or absence of CN with lid closure or darkness that lack a description of the instructions to the subject provide no useful information.

The recognition of CN is of extreme importance, particularly in the adult patient, and may obviate unnecessary and never shows more than minor amplitude dissociation between the two eyes. Clinically, the nystagmus usually appears uniplanar. Like vestibular end-organ nystagmus, horizontal nystagmus remains horizontal when the eyes are deviated vertically and does not convert to vertical nystagmus. Using new, sensitive techniques for recording torsional eye movements, we have found small but significant tensional components in the CN of subjects previously thought to have purely horizontal CN. Because the prominent horizontal movement masks the usually smaller torsional component, the latter appears to be a common characteristic of "horizontal" CN. In most patients, rightward movements were accompanied by clockwise torsion and leftward movements by counter clock wise torsion.

Eye movement recordings of CN occasionally show a pure pendular waveform (sinusoidal) or a saw-toothed waveform ((sinusoidal) or a saw toothed wave form (Equaimplitude linear slow phase with fovea ting saccade) typically seen in vestibular nystagmus. These pure forms are neither frequent nor path gnomonic for CN. More often, CN manifests distinctive waveforms that have not been reported in acquired nystagmus. These waveforms are an _expression of the attempts by the ocular motor control system to increase foveation me imposed on inherently unstable slow control. For pendular waveforms, the target is foveated at the peaks that are more flattened, indicating extended foveation. Extended foveation in an adult with lifelong nystagmus secondary to a congenital brain stem hamar " toma, and in an adult given gabapentin for treatment of nystagmus secondary to an arteriovenous malformation," supports the hypothesis that extended foveation periods in CN represent the action of a normal fixation system on the underlying CN oscillation.

Increased foveation time is the most effective determinant of increased acuity.23-;6 In most CN subjects, the / best waveform (i.e., most foveation time per cycle) is in

The null region associated with a particular gaze or convergence angle, but in other subjects it is not: these latter subjects prefer the gaze or convergence angle that yields the best waveform, even if it is not the wave form new type of surgery that shows promise in damping the CN of subjects that do not have either a gaze-angle or a convergence null. have a primary-position null, or do not have a static null they have /asymmetric (a)periodic alternating CN The surgery consists of a simple tenotomy, dissection, and suture of the involved extra ocular muscles in place, with neither recession nor resection for patients with both convergence and gaze-angle nulls, exploitation of the former (surgically or with Vergennes Prisms usually damps the CN and increases acuity most; it is necessary to add -1.00 S both eyes (OU)] to vengeance prisms for pre-presbyopic patients.

Afferent stimulation can be used in all patients, regardless of the presence of nulls, who exhibit CN damping with active stimulation (see below)

Signs and symptoms of Congenital Nystagmus

Binocular with similar amplitude in both eyes

Provoked or increased by fixation attempt

Gaze-modulated, not gaze-evoked

Diminished (damped) by gaze or convergence

Usually horizontal and torsional (vertical rare)

Increasing velocity slow phases

Distinctive waveforms (foveation periods and braking saccades)

Superimposition of latent component possible "Inversion" of the opt kinetic reflex (actually, CN reversal) Associated head oscillation or turn No oscillopsia  Aperiodic alternation possible (Baclonfen ineffective) ^r Abolished in sleep or inattention to visual tasks

Treatment for Congenital Nystagmus 

If the CN nulls ONLY with gaze

Resection and recession (OU

Version prisms 

Afferent stimulation (passive or active) 

If the CN nulls ONLY with convergence 

Bimedial recession (artificial divergence)

Vergence prisms with -1.00 S (OU)

Afferent stimulation (passive or active) If the CN nulls with BOTH gaze and convergence

Bimedial recession alone or combined with resection and recession Vergence or composite prisms with -1.00 S (OU)

Afferent stimulation (passive or active) If the CN nulls with NEITHER gaze nor convergence or is asymmetric aperiodic alternating CN

Tenotomy, dissection, and suture* (OU)

Maximal recession (OU)

Afferent stimulation (passive or active)

Patients with CN usually do not experience an illusory oscillatory movement of their environment (oscillopsia). This lack of oscillopsia in CN, and also in LMLN, suggests that both oscillations occur within an efference copy feedback loop that serves to nullify the effects of retinal-image oscillation induced by either of these instabilities.'3^ Like most ocular oscillations (myoclonus being the exception), CN disappears in

During fixation of stationary targets, many patients with CN have a permanent null region representing the gaze angle at which the intensity of the nystagmus is the lowest they often turn their heads to permit straight-ahead viewing with the eyes in the null region. Such patients benefit from appropriate prism spectacles that alleviate the necessity for the head turn and the resulting increased fixation attempt.14'23

Some CN patients may exhibit a "superimposed latent" component that induces null shifts toward an eye that is covered Demonstration of such a shift and maintenance of any of the CN waveforms establish the nystagmus as congenital rather than latent. Rarely, a null shift is toward the viewing

In many subjects with CN, afferent stimulation of the ophthalmic division of the trigeminal nerve or of the neck may damp the nystagmus allowing increased visual acuity.3144 Neck or forehead vibration prolonged foveation periods, yielding higher values of the NAF and improved visual acuity in 9 of 13 patients with CN.31 This non-invasive and benign therapy (active afferent stimulation) may prove useful in both CN and acquired nystagmus. The use of soft contact lenses to improve the acuity of individuals with CN takes advantage of the damping effect on CN of (passive) afferent stimulation.45-48

Soft contact lenses are not contraindicated in CN and can provide better acuity than spectacles in patients whose CN damps with afferent stimulation. Piano soft contact lenses can be used if no refractive correction is required. I

Relatives of patients with CN may have saccadic instabilities,49 and carriers of blue-cone monochromatism may have vertical (upbeat and downbeat) nystagmus and LMLN.50

Abducens Palsies

It is not proper to equate all lateral rectus malfunction with “sixth nerve Palsy to do so confuses the confuses the issue and lead to inappropriate diagnostic procedure. example, myasthenia. Graves' (dysthyroid) myopalhy. Or orbital inflammation may all produce deficits of abduction, none of which is due to sixth nerve lesions. The "neural" etiology of lateral rectus weakness must be established or. At least, other causes excluded when possible P:atate°43^.). Along with details provided by a thorough medical history, special diagnostic techniques should always be employed, including intravenous edro-phonium (Tensilon), forced duction and forced generation tests. Until local orbital diseases have been excluded, it is premature for the ophthalmologist to refer a patient for a "neurologic workup."

 pathophysiology

 The causes of actual sixth nerve palsy are legion As noted previously, the peripheral course of the abducens nerve is a lengthy one that predisposes this cranial nerve to involvement at all levels, from the brain stem and base of the skull, through th

Causes of Sixth Nerve Palsies

Nonlocalizing 

Increased intracranial pressure

Intracranial hypotension

Head trauma 

Lumbar puncture or spinal anesthesia vascular, hypertension Diabetes/microvascular

Para infectious processes (postwal; middle ear infections in

Children) Basal meningitis

Localizing

Pontine syndromes (infarction, demyelination, tumor); contra lateral hemiplegia;

ipsilateral facial palsy, ipsilateral horizontal gaze palsy (± ipsilateral intemuclear

ophthal-moplegia); ipsilateral facial analgesia Cerebellopontine angle lesions

(acoustic neuroma, meningi-oma): in combination with disorders of the eighth,

seventh, and ophthalmic-trigeminal nerves (especially corneal hypoesthesia),

nystagmus, and cerebellar .signs

Clivus lesions (nasopharyngeal carcinoma, clivus chordoma)

Middle fossa disorders (tumor, inflammation of medial aspect of petrous): facial pain/numbness, = facial palsy

Cavernous sinus or superior orbital fissure (tumor, inflammation, aneurysm): in combination with disorders of the third, fourth, and ophthalmic-trigeminal nerves (pain/ numbness)

Carotid-cavernous or dural arteriovenous fistula

Causes of abduction deficits

Sixth nerve palsies

Graves' myopathy (fibrotic medial rectus)

Myasthenia gravis .

Orbital pseudotumor / myositis 

Orbital trauma (medial rectus entrapment) Congenital defects (Duane, Mobius syndromes) "Convergence spasm" (spasm of the near reflex)





Diagnostic studies for lsolaed Abduction palsy


Tensilon test

Forced ductions/forced generations

Serum glucose: fasting or after glucose load, or

glycosylated hemoglobin

Imaging studies

Contrast- enhanced CT: axial and coronal views espe-

cially of orbital apex, cavemous sinus sella and clivus

Contrast enhanced MRI: cavemous sinus, clivus


Pain or mild ocular discomfort may occur with onset of ischemic diabetic abducens palsy. If pain persists or woresnes imaging studies should be performed.


Although it is true that some isolated “ chronic” sixth never pareses last longer than 6 month yet follow a completely being course other are indeed caused by potentially treatable basal tumors. When pain persists and all radio logic and orbital in vestigation are unrevealing a trial of corticosteroids (e.i.60 mg prednisone orally for 5 days) may result in prompt and dramatic relief in witch case a tentative diagnosis of nonspecific inflammation of the superior orbital fissure or cavernous sinus may be made. How ever the response to steroid trial may produce relief of pain with neoplasm’s as inflammation. Certainly unrelenting eye or orbital or facial pain is an indication for exquisite visualization of the cavernous sinus and parasellar area by thin-sec-tion MRI scanning and either magnetic resonance or conventional angiography if vascular abnormalities are suspected. Isolated sixth nerve palsies in children often resolve spontaneously. Newborns may manifest a tran-sient lateral rectus weakness.with resolution occurring by 6 week. Symptomatic treatment of an acute sixth nerve palsy includes the use of fresnel prisms or alternate patching o avoid diplopia and possible medial rectus contracture. The injection of botulinum toxin type A(Botox) is quite effective at prevening muscle contrac true and improving fusion in the primary position of garz. However, this procedure carrier the disadvantage of significant


Crossed diplopia (exotropia) in contra lateral gaze. Defimtive surgical correction of a sixth nerve paresis has been stable for at least 6 month. The primary consideration in these cases is the amount of residua abducing power of the lateral rectus since moderate to good abduction is associated with successful ipsilateral recess/resect procedures. However if residual medial rectus recession may be combined with cither a full or partial thickness tendon transplant procedure of the superior and inferior recti or a Jensen procedure. The latter may have a decreased disk of anterior segament ischemia in susceptible patients. Any puzzling acquired ocular motility distur bance with or without ptosis but with clinically normal pupils should raise the question of myasthenia. Myasthenia may be characterized as follows; weakness without other signs of neurologic deficit (no reflex changes sensory loss or muscle atrophy); variability of muscle function within minutes hours or week remission and exacerbations ( sometimes triggered by infection facial fever or trauma); and tendency o affect extraocular facial and or pharyngeal muscles. In addition there is usually reversal or improvement of muscle function with cholinergic drugs. The onset of myasthenia may occur at any age, but before age 40 the disease is more common in woman. Neonatal froms are rarely encountered and he clinical course in children and infants differs from adults demonstrating a wider spectrum of myasthenic syndromes. The association with thymoma is well known (approximately 10% of myasthenia patients), and in such patients morbidity tends to be more severe and mortality rates are higher; In addition dysthyroidism is found in approxi mutely 5% of myasthenic patients such that ocular signs may be admixed (e.i.exophthalmos and ptosis paretic and restrictive motility defects). There is also a distinct relationship between collagen vascular disorders thy moma and myasthenia and a familial incidence of my asthenia has been reported.

Myasthenia gravis is an autoimmune disorder characterized by a reduction of available postsynapitc acetylcholine recepotors on the end plates of the neuromuscular trasmisson and subsequently destroy the receport complex. The humoral immune response (e.g.polyclonal LgG produced by B Iynphcoytes ) apparently plays a critical role in producing this disease. Antiacetycholine receptor antibody is said to be present in 85% to 90% of patients with generalized myasthenia gravis (GMG) but less in patients with myasthenia "restriced" to ocular muscles ( OMG ). Indeed given the "embryonic" tyep of acetylcholine receptor in ocular muscles there is evidence for consid erable of " sero-negative" OMG.Although actual antibody titers correlate poorly wuth the severity of the disease, antibodies do accelerate degradation of acetylcholine receptors and increase the extent of receport blockade. In trun incereased receptor degardation and blockade correspond closely with clinical status and thus confirm the relevance of antiacetylcholine receptor antibodies in the pathogenesis of myasthenia.Thus the concept of a "safeety margin " is important in the pathophysiology of myasthenia. Normally both acetycholine receptors and acetylcholine molecules at the neuromuscular junction are in significant excess. Any aberration that decreases the likelihood of molecular interaction between these two entities reduces this safety margin and produces clinical symptoms. The cause of autoimmune attack on acetylcholine receptor is not known. but the thymus regulary shows prominent germinal centers (presumably the source of antibody forming cells). if not actual tumoral growth. Epithelial ( "myoid" ) cellsw normally present in the thymus do indeed histogically receptors; these cells may become antigenic.Ocular mucle involvement eventually occurs in 90% of all myasthenia and accounts for the initial complaint in approximately 75%. since muscle fatigability and remissions are the hall marks of the disease it is not surprising that cular signs may vary, lasting from a period of hours to a course is almost invariable it may at first be unilateral and noted only as the day or the fatigue progresses.

Diagnostic procedures

that complement Tensilon and prostigmin testing particularly in generalized myasthenia include (1) electromyography (EMG) of muscle action potentials evoked by repetitive supramaximal nerve stimulation (approximately 3 to 5 Hz) and for the presence of the jitter phenomenon on single muscle fiber studies; and (2) antiacetycholine receptor antibody titer (see above). In OMG, testing of the orbicularis muscles may be helpful. The relative importance of several methods stimulated single fiber EMG ( stimulated SFEMG), repetitive nerve stimulation test (RNS) of orbicularis oculi muscle, and infrared reflection oculography (IROG) was investigated based on the results os thwe three neurophysiologic tests the patients can be divided into three groups;


Group 1: Those with an abnormal stimulated SFEMG, abnormal RNS, and /or abnormal IROG


Group 2: Those with only a slightly abnormal stimulated SFEMG


Group 3: Those with normal results in all tree tests


A diagnosis or firm suspicion of myasthenia on the part of the ophthalmologist is an indication for thorough examination by a neurologist. Thin section contrast enhanced CT scan or MRI of the mediastinum should be performed to search for patients with only thymoma. Ideally tests to determine thyroid function and the presence of collagen vascular disease should be performed. The pharnacologic treatment of myasthenia ocular or otherwise is beyond the purlieu of even the interested ophthalmologist and is strictly the domain of an experienced neurologist who would be more familiar with the response of myasthenics to the primary disorder and with the difficulties of dose variations and medication schedules. The ophthalmologist should collaborate by reevaluating orutches when indicated. Large variable or incomitant deviations are best treated with an opaque lens. Ptosis surgery is dangerous because defective ocular motility can lead to problems of corneal exposure.


Treatment

for myasthenia at present is somewhat individualized but is based on one of the following options: (1) increasing the amount of acetylcholine available with cholinesterase especially for the oftenresistant ocular symptoms or less frequently with immunosuppressive agents (e.g,azathioprine, cycolosporine ) plasmapheresis and/or thymectomy. Gamma globulin therapy and plasmapheresis are rarely if ever indicated for purely ocular myasthenia. Other pharmacologic agents include ambenonium a biquaternary compound that binds irreversibly to acetylcholinesterase, with a duration of approximately 8 hours.

References:

WALSH AND HOYTs clinical neuroopthalmology

Williams and wilkins, current neuroopthalmology

Color atlas and clinical synopsis of ophthalmology, peter savino

Atlas of neuro ophthalmology Thomas c spoor

www.uiowa.edu

www.med1.de/experten/diskussion/opthalmologie