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Triatoma live in warm climates, especially in the southwestern and southeastern United States, Texas, and the Gulf states. Allergy to these biting insects is uncommon, and anaphylactic reactions usually occur in individuals with repeated bites. Treatment of allergic reactions to biting insects is directed to symptomatic management of the acute reaction and to avoidance precautions, as with Hymenoptera sensitivity. In the case of Triatoma allergy, immunotherapy using a salivary gland extract was demonstrated to be effective. The natural history and epidemiology of insect sting allergy: clinical implications. Outcomes of allergy to insect stings in children with and without venom immunotherapy. Unpredictable reactions are unrelated to the pharmacologic activity of the drug, occur in susceptible individuals, and are generally not dose dependent. The term drug allergy has been used by some to describe only IgE-mediated drug reactions. Currently, three hypotheses have been proposed to explain immunologic mechanisms of drug allergy. The hapten hypothesis explains how small molecules that would typically be nonimmunogenic can result in sensitization and allergy. The prototypical example is sulfamethoxazole, which itself is not protein reactive but gains reactivity through liver 4 metabolism eventually to a nitroso intermediate (N -sulfonamidoyl), which covalently haptenates human serum proteins. Carbamazepine is an example of a drug that elicits a strong T-cell response but no antibodies indicative of a p-I interaction. Many drug reactions can be readily classified using the Gell and Coombs system of hypersensitivity. Type I immediate reactions to drugs are another common form of drug allergy and are mediated by drug-specific IgE antibodies. Clinical manifestations of type I reactions may include urticaria, angioedema, bronchospasm, and anaphylaxis. Cytotoxic drug reactions most commonly affect cells of the hematopoetic system and may present as hemolytic anemia, thrombocytopenia, or granulocytopenia. Several other well-characterized immunologic reactions to drugs have been described, which do not fit into the Gell and Coombs hypersensitivity paradigm. Pseudoallergic reactions resemble type I hypersensitivity clinically but are not caused by IgE-mediated reactions. The pathogenesis of pseudoallergic reactions relates to IgE independent mast cell activation. Drugs may also cause complement activation, release of bradykinin, or other innate immune responses. Drug induced vasculitis, drug-induced granulomatous disease, and drug-induced lupus may be organ specific or have multiorgan involvement. Oral administration appears less likely to elicit allergic reactions compared to parenteral or cutaneous administration. Higher doses and more frequent, repetitive administration are associated with greater sensitization. Host risk factors for drug allergies include female gender and concurrent medical illnesses. Abacavir is a nucleoside reverse transcriptase inhibitor that has been associated with a multiorgan hypersensitivity reaction in approximately 4% of patients. Symptoms and signs of abacavir hypersensitivity include fever, rash, malaise, and gastrointestinal and * respiratory symptoms. Table 15-1 outlines specific drugs and alleles associated with severe drug reactions. It is important to note that pharmacogenetics are dependent on the specific drug and, in some cases. Exanthems the most common cutaneous manifestation of drug allergic reactions is a generalized exanthem (a. These lesions are pruritic, often beginning as macules that can evolve into papules and eventually may coalesce into plaques. Drug induced exanthems are pru-ritic and typically involve the trunk and spread outward to the limbs in a bilateral symmetric pattern. Many drug-induced exanthems are considered delayed-type hypersensitivity reactions and typically evolve after several days of being on the offending drug. This should be distinguished from the type of epidermal detachment seen in severe cutaneous reactions that occurs early in the reaction. Drug-induced exanthems do not evolve into anaphylactic reactions as they are not IgE-mediated reactions. Urticaria and angioedema Urticaria and angioedema are the most common manifestations of IgE-mediated drug allergy. Urticaria is the most common manifestation of serum sickness; however, the presence of maculopapular lesions of the sides of the fingers and toes or a serpiginous distribution of such lesions along lateral aspects of both soles may be more specific for serum sickness. Urticarial lesions are raised, erythema-tous, pruritic lesions that wax and wane and range in size from a few millimeters to several inches in diameter. Angioedema presents as swelling of the tissues and may not be pruritic or erythematous. Fixed drug eruptions Fixed drug eruptions recur at the same skin or mucosal site upon reintroduction of the causative drug. Fixed drug eruptions typically develop within 1 to 2 weeks of drug exposure but may recur more rapidly with subsequent reexposure. Fixed drug eruptions are pleomorphic and may present as eczematous lesions, papules, vesicles, or urticaria. Lesions are often round or oval, sharply demarcated, red to livid, slightly elevated plaques, ranging from a few millimeters to several centimeters in diameter. Fixed drug eruptions have a predilection for the lips, hands, and genitalia (especially in men). Fixed drug eruptions can occur with a number of medications including tetracycline, nonsteroidal anti inflammatory drugs, and carbamazepine. Biologics such as infliximab may cause eczematous lesions with a similar distribution as atopic dermatitis. Exfoliative dermatitis Exfoliative dermatitis is characterized by widespread erythroderma and marked scaling involving >90% of the skin surface. Several systemic manifestations can occur including hypothermia, edema, anemia, leukocytosis, and hypoalbuminemia. Photoallergic reactions typically develop within days of drug and ultraviolet light exposure. Phototoxic reactions typically present with erythroderma within minutes to hours of sunlight exposure but may present with vesicles with severe reactions. Drug-induced cutaneous lupus may also present with eruptions in a photodistribution, typically with erythema, or scaly, annular plaques. Lichenoid eruptions Some drug reactions may manifest as lichenoid reactions with violaceous, polygonal papules. Pustular drug eruptions Several cutaneous drug reactions may present with pustules. Acne can occur with glucocorticoids, androgens, lithium, phenytoin, and iso-niazid and is quite common with the immunosuppressant sirolimus.

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Leishmania can develop resistance highest cure rate in kala-azar: up to 99% clinical to miltefosine and this may be due to mutation and parasitological cure has been reported from limiting transport of the drug into the parasite cell. In the early phase, t is ~7 days while the Combination therapy terminal t is ~ 4 weeks. Clinical studies in India have testified to the high efficacy of drug combinations, and have shown 4. Paromomycin this aminoglycoside anti that duration of treatment can be reduced by half biotic is described with antiamoebic drugs on or more. Miltefosine (oral) daily 10 days + India and Africa for kala-azar and found to be Paromomycin. Paromomycin (15%) ointment: applied leishmaniasis (oriental sore) topically on the sore, twice daily for 20 days. Dermal leishmaniasis is not a life-threatening Small and mild lesion may heal by itself in a few condition; many cases are treated by local months. Sodium stibogluconate: Infiltrate 2 ml of the Antibiotics may be needed for secondary solution (100 mg antimony/ml) round the sore. Palpation of abdomen revealed soft tender enlargement of liver 2 cm below costal margin. A clinical diagnosis of amoebic liver abscess was made and he was treated with: Injection Metronidazole 500 mg i. The injections were substituted by oral metronidazole 800 mg 3 times a day for another 5 days, and the patient became well, except weakness and mild tenderness in the right lower chest. Treatment after resection of the cyst Helminthiasis is prevalent globally (1/3rd of may prevent its regrowth. It binds to tubulin of suscep of many helminths, but some also live in tissues, tible worms with high affinity and inhibits its or their larvae migrate into tissues. Intracellular microtubules in the the host by depriving him of food, causing cells of the worm are gradually lost. In addition, blood loss, injury to organs, intestinal or it probably blocks glucose uptake in the parasite lymphatic obstruction and by secreting toxins. Hatching of Helminthiasis is rarely fatal, but is a major cause nematode eggs and their larvae are also inhibited. Develop absorbed is excreted mainly as inactive ment of resistance has not been a problem in metabolites in urine/faeces. The current choice of drugs for worm infestations common Adverse effects Mebendazole is well tolerated in the Indian subcontinent is given in Table 61. Diarrhoea, nausea and abdominal pain have attended its use in heavy Mebendazole infestation. Incidents of expulsion of Ascaris from mouth or nose have occurred, probably due It is a benzimidazole introduced in 1972. It has produced nearly 100% cure not known, but it is contraindicated on the basis rate/reduction in egg count in roundworm, hook of animal data. No fasting, purging or any other drug to metronidazole for facilitating extraction Whipworm preparation of the patients is needed. Upto 7 day treatment may be needed in heavy Mebendazole is one of the preferred drugs trichuriasis for treatment of multiple infestations and is more Pin worm (Enterobius) 100 mg single dose, effective than albendazole in trichuriasis. It is a subsequently introduced congener of this holds true of enterobiasis, irrespective of mebendazole: retains the broad-spectrum activity drug used. Efficacy in strongy In strongyloidosis, it is more effective than loidosis is low, and it is the 2nd choice drug mebendazole: a 3 day course has achieved nearly to ivermectin. Three day adult worm from intestine, but has limited treatment has been found necessary for tapeworms effect on larvae that have migrated to muscles. Results in hydatid disease They are not killed but symptomatic relief and hookworm have been superior to mebendazole. Corticosteroids are added if systemic Albendazole has weak microfilaricidal action, kills manifestations are severe. Cysticercosis of other tissues Pharmacokinetics Absorption of albendazole (muscles, subcutaneous area) also responds, after oral administration is significant, but but no drug should be given for ocular inconsistent. It is the preferred treatment given before distributed in the body, enters brain and is and after surgery as well as to inoperable cases. For intestinal worms it Thiabendazole should be given on empty stomach, while for It was the first benzimidazole polyanthelmintic introduced in 1961, which covered practically all species of nematodes cysticercosis, hydatid and cutaneous larva infesting the g. Thiabendazole has gone out of use, due to the because of the availability at more convenient and better availability of better tolerated mebendazole and albendazole. Flaccid paralysis occurs and worms infestation in children; use soon extended to are expelled alive. Therefore, often a purgative (senna) is given with it, against Ascaris, Enterobius and Ancylostoma is but is not necessary. Lower cure rates (about 60%) have been obtained A considerable fraction of the oral dose of piperazine is in case of Necator infestation. It is contraindicated in renal insufficiency cholinergic receptors in the worms resulting in and in epileptics, but is safe in the pregnant. Because of its capacity to relax ascarids, it is of particular value in intestinal obstruction due to been demonstrated. It can be used during pregnancy while other hyperpolarization and flaccid paralysis, it drugs cannot be used. Levamisole, Tetramisole Adverse effects Pyrantel pamoate is remark Tetramisole was developed in the late 1960s. It is racemic; its levo isomer (levamisole) was found to be more active and is ably free of side effects: occasional g. Both are active against many nematodes, but symptoms, headache and dizziness is reported. Interference with carbohydrate metabolism (inhibition of fumarate reductase) may women and in children below 2 years has not also be contributing. It is less Ancylostoma and Enterobius: a single dose of effective against Neccator: not indicated. Levamisole is an immunomodulator as well: restores depressed No fasting, purging or other preparation of the T cell function. Excretion is faster benefit probably reflects anti-microfilarial action: in acidic urine.

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Peripheral vision is affected first but eventually the entire vision will be lost if not treated. Combination topical therapy; this is instituted whenever it is observed that one drug is no more effective. Uncontrolled glaucoma despite maximal medical therapy and laser trabeculoplasty 2. It is characterized by apposition of peripheral iris against the trabecular meshwork resulting in obstruction of aqueous outflow by closure of an already narrow angle of the anterior chamber. This is the most common in people over 40years of age and usually affects one eye. This assessment facilitates better opportunities to provide more detailed information in relation to the perioperative management of cataract for patients. Increased patients involvement and subsequent cooperation in care planning lead to the negotiation of much more flexible approaches to perioperative care. Dystrophies occur bilaterally, manifesting occasionally at birth, but more usually during first or second decade and sometimes even later in life. Onset occurs at puberty; the condition may progress for more than 20 years and is bilateral. Blurred vision due to progressive myopia and irregular astigmatism is a prominent symptom which does not improve fully despite full correction with glasses. The donor eye should be removed within 6 hours of death and should be stored under sterile conditions. In myopia the corneal surface is flattened so that the image focuses onto the retina. It is used for patients with superficial corneal scars, corneal degenerations, and recurrent corneal erosions. This type of retinal detachment can also be precipitated by moderate trauma, such as stooping or lifting weights, or by direct trauma to the eye. It occurs when fibrous tissue in the vitreous humor attaches to the sensory retina and, as it contracts, pulls the retina away from its normal position, as seen in patients with sickle cell disease or diabetes mellitus. Any condition that weakens the retina such as lattice degeneration of the retina 2. Myopia the globe is big in size resulting in the thinning of the wall leading to detachment 5. Rest strict bed rest to allow the retinal detachment to subside before surgery is carried out. Stage 2: the line structure in stage 1 acquires a volume to form a ridge with height and width Stage 3: the ridge with extra-retinal fibrovascular proliferates into the vitreous. It is a leading cause of blindness in developed countries, in population above the age of 65years. Common risk factors which may affect age of onset and/or progression include heredity, nutrition, and smoking, and hypertension, exposure to sunlight, hyperopia, blue eyes and cataract It is of two types; 1. It includes examination of the anks, begins with inspection for scars, masses, or hernias. Examination of the back should be performed to check for scars and scoliosis which may be an indication of potential spine abnormalities that may contribute to dysfunction of the urinary system. Supra pubic palpation is performed to determine if the patient has a distended bladder or pelvic mass. This is rst done in lithotomy position and may be repeated with the patient standing. The urethral meatus should be observed and the urethra palpated for any abnormalities. This can be aided by applying slight pressure wall with the posterior blade of a small vaginal speculum. The position of the urethra, bladder neck, and bladder can be observed at rest and with straining to evaluate support of these structures and determine the presence of urethral hypermobility and cystocele. Also with coughing and straining, the urethra should be observed for urine loss and whether that loss occurs with hypermobility. The uterus and cervix should be evaluated at rest and with straining to determine prolapse. Bimanual examination is done to evaluate the presence of uterine, adnexal, or other pelvic masses. This is often best accomplished by rst retracting the anterior vaginal wall and then the posterior wall. Finally the posterior vaginal compartment is examined by retracting the anterior vaginal wall with the speculum blade. Urine analysis; Urinalysis can screen for pyuria, bacte-uria hematuria, and the presence of glucosuria or proteinuria. When abnormalities are found on urine analysis, further testing may be conducted suchas urine culture. A urinalysis (urine analysis) is a commonly performed diagnostic test for the renal system. Urinalysis is an invaluable tool in the diagnosis of kidney disease and other systemic diseases that may affect the kidneys. The results of the urinalysis give information regarding kidney function and various body functions. A routine urinalysis specimen may be collected at any time of day; however, the first morning specimen is best. First morning specimens are usually concentrated and more likely to contain abnormal constituents if they are present. Urine collected for cytology should not be a first morning specimen due to changes in epithelial cells in urine held overnight. The patient is instructed to begin to void into the toilet, and then move the collection container under the stream, and then finish voiding into the toilet. Female patients should be told to separate the labia with one hand and keep them separated while washing and collecting the specimen to decrease the risk of contamination of the specimen. If the female patient is menstruating, this should be specified on the laboratory form. The uncircumcised male patient should be directed to retract the foreskin with one hand and keep it retracted while cleansing and voiding. If a urinalysis is ordered for a patient with a urinary catheter, the nurse obtains the urine specimen. This specimen is considered sterile because it is coming directly from the bladder into the urinary catheter tubing. To obtain the specimen, wear clean gloves and use an alcohol swab to clean the sample port on the catheter tubing. Insert a blunt needle of a syringe (usually 10 mL) into the port and withdraw urine from the tubing into the syringe. Then empty the urine from the syringe into a collection container and safely dispose of the syringe. Composite urine specimens are collected over a period of time that may range from 2 to 24 hours. These specimens are usually used to examine the urine for specific components such as glucose, electrolytes, protein, 17-ketosteroids, catecholamines, creatinine, and minerals. These specimens may need refrigeration or may have preservatives added to the collection container. At the end of the time frame, the patient is asked to void and this is added to the container as the last amount to be added. Urine culture; it is conducted in cases of suspected infection or urine cytology, endoscopic, and radiographic studies when microscopic hematuria is present. In some select cases, more specic blood and urine testing may be performed, but these are usually dependent on patient history and physical as well as the results of simple tests. A voiding and intake diary or an intake and output record; a record of intake and output provides a baseline to assess future treatment.

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The lower lid has three anatomically distinct fat pads beneath the orbital septum. As it enters the lid, it forms an aponeurosis that attaches to the lower third of the superior tarsal plate. A crease usually present in the mid position of the upper lid in Caucasians represents an attachment of levator aponeurosis fibers to the more superficial layers. In the lower lid, the capsulopalpebral fascia originates from the inferior rectus muscle and inserts on the inferior border of the tarsus. Conjunctiva lines the inner surface of the lids and forms the blind cul-de-sacs of the upper and lower fornices as it reflects onto the eye. Most hordeola are caused by staphylococcal infections, usually Staphylococcus aureus. If the process does not begin to resolve within 48 hours, incision and drainage of the purulent material is indicated. A vertical incision should be made on the conjunctival surface to avoid cutting across the meibomian glands. If the hordeolum is pointing externally, a horizontal incision adjacent and parallel to the eyelash line should be made on the skin to conceal the incision. Symptoms begin with mild inflammation and tenderness that persists over a period of weeks to months. Most chalazia point toward the conjunctival surface, which may be slightly reddened or elevated. Intervention is indicated if the lesion is not amenable to a warm compress regimen, distorts the vision, or is aesthetically unacceptable. Pathology studies are seldom indicated, but on histologic examination, there is proliferation of the endothelium of the acinus and a granulomatous inflammatory response that includes Langerhans-type giant cells. Biopsy is, however, indicated for recurrent chalazion, since sebaceous cell carcinoma may mimic the appearance of chalazion. Surgical incision and drainage is performed via a vertical incision into the tarsus from the conjunctival surface followed by curettement of the gelatinous 161 material and glandular epithelium. Intralesional steroid injections alone may be useful for small lesions and in combination with excision for more chronic cases. Staphylococcal blepharitis may be due to infection with S aureus, Staphylococcus epidermidis, or coagulase-negative staphylococci. Seborrheic blepharitis is usually associated with the presence of Malassezia furfur (formerly known as Pityrosporum ovale), although this organism has not been shown to be causative. The chief symptoms are irritation, burning, and itching of the eyes and lid margins. In the staphylococcal type, the scales are dry, the lids are erythematous, the lid margins may be ulcerated, and the lashes tend to fall out. In the seborrheic type, the scales are greasy, ulceration does not occur, and the lid margins are less inflamed. In the more common mixed type, both dry and greasy scales are present with lid margin inflammation. Staphylococcal species and M furfur can be seen together or singly in stained material scraped from the lid margins. Staphylococcal blepharitis may be complicated by hordeola, chalazia, epithelial keratitis of the lower third of the cornea, and marginal keratitis (see Chapter 6). Treatment consists of lid hygiene, particularly in the seborrheic type of blepharitis. Scales must be removed daily from the lid margins by gentle mechanical scrubbing with a damp cotton applicator and a mild soap such as 162 baby shampoo. Staphylococcal blepharitis is treated with antistaphylococcal antibiotic or sulfacetamide ointment applied on a cotton applicator once daily to the lid margins. Both types may run a chronic course over a period of months or years if not treated adequately. Associated staphylococcal conjunctivitis or keratitis usually disappears promptly following local antistaphylococcal medication. Colonization or frank infection with strains of staphylococci is frequently associated with meibomian gland disease and may represent one reason for the disturbance of meibomian gland function. Bacterial lipases may cause inflammation of the meibomian glands and conjunctiva and disruption of the tear film. Posterior blepharitis is manifested by a broad spectrum of symptoms involving the lids, tear film, conjunctiva, and cornea. Meibomian gland changes include inflammation of the meibomian orifices (meibomianitis), plugging of the orifices with inspissated secretions, dilatation of the meibomian glands in the tarsal plates, and production of abnormal soft, cheesy secretion upon pressure over the glands. The lid margin demonstrates hyperemia and telangiectasia and may become rounded and rolled inward as a result of scarring of the tarsal conjunctiva, causing an abnormal relationship between the precorneal tear film and the meibomian gland orifices. Primary therapy is application of warm compresses to the lids, with periodic meibomian gland expression. Further treatment is determined by the associated conjunctival and corneal changes. Topical therapy with antibiotics is guided by results of bacterial cultures from the lid margins. Frank inflammation of the lids calls for anti-inflammatory treatment, including long-term therapy with topical Metrogel (metronidazole, 0. Tear film dysfunction may necessitate artificial tears with a preference for preservative free formulations to avoid toxic reactions. Involutional entropion is the most common and by definition occurs as a result of aging. It always affects the lower lid and is the result of a combination of horizontal lid laxity, disinsertion of the lower lid retractors, and overriding of the preseptal orbicularis muscle. Cicatricial entropion may involve the upper or lower lid and is the result of 164 conjunctival and tarsal scar formation. It is most often found with chronic inflammatory diseases such as trachoma or ocular cicatricial pemphigoid. Congenital entropion is rare and should not be confused with congenital epiblepharon, which often presents in Asians. In congenital entropion, the lid margin is rotated toward the cornea, whereas in epiblepharon, the pretarsal skin and orbicularis muscle cause the lashes to rotate around the tarsal border. Trichiasis is misdirection of eyelashes toward the cornea and may be due to epiblepharon or simply misdirected growth. Chronic inflammatory lid diseases such as blepharitis may also cause scarring of the lash follicles and subsequent misdirected growth. Distichiasis is a condition manifested by accessory eyelashes, often growing from the orifices of the meibomian glands. It may be congenital or the result of inflammatory, metaplastic changes in the glands of the lid margin. Correction of involutional entropion may be achieved by a number of approaches with consideration for horizontal lid tightening, repair of the lower lid retractors, or rotation of the lid margin. Useful temporary measures include taping the lower lid to the cheek, injection of botulinum toxin in the pretarsal orbicularis, or performing rotational lid sutures. Cicatricial entropion repair depends on the degree of severity with the option of skin resection for mild disease, tarsal infracture or margin rotation for moderate disease, and scar tissue release with grafting of the posterior lid for severe disease. Trichiasis without entropion can be temporarily relieved by epilating the offending eyelashes. Permanent relief may be achieved with electrolysis, laser, cryotherapy, or lid surgery. Cicatricial ectropion is caused by contracture of the skin of the lid from trauma or inflammation. Symptoms of tearing and irritation resulting in exposure keratitis may occur with any type.

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These have a dilated and tortuous lumen, a complete absence of muscular and elastic tissue, no continuous endothelial lining, mural thrombi and fibrinoid deposition. It has been reported to occur in two stages: the first wave of trophoblastic invasion converts the decidual segments of the spiral arteries in the first trimester and the second wave converts the myometrial segments in the second trimester 5. Browne and Veall injected 24 Na tracer directly into the choriodecidual space of women with anterior placentae and used a Geiger counter to construct decay curves for the falling levels of radioactivity 7. Although this method was beset by technical failures, it established the commonly quoted figure of 600 ml/min for uterine blood flow at term. Validation of the method was performed by directing a pulsed wave Doppler facility along the same line and obtaining identical waveforms from subplacental vessels. The Doppler probe was directed into the parauterine area in the region of the lower uterine segment and rotated until a characteristic waveform pattern was recognized. In the early stages of the study, the methodology was validated with Duplex equipment or by in vivo measurements obtained during Cesarean section. They found that patterns of uterine, arcuate and iliac vessels could be differentiated from each other and from other vessels in the pelvis. The presence of an early diastolic notch was noted and was found to disappear between 20 and 26 weeks. Color flow imaging was used to visualize the flow through the main uterine artery medial to the external iliac artery (Figure 2) and the Doppler sample gate was placed at the point of maximal color brightness. Color flow imaging was found to allow a higher number of reliable recordings to be obtained, to shorten the observation time, and to reduce the intra and interobserver coefficients of variation. Normal flow velocity waveforms from the uterine artery at 24 weeks of gestation demonstrating high diastolic flow (right). Impedance in the uterine artery on the same site as the placenta is lower, which is thought to be due to the trophoblastic invasion only taking place in placental spiral arteries and the fall in impedance engendered by this being transmitted to other parts of the uterine circulation through collaterals. Flow velocity waveforms from the umbilical cord have a characteristic saw-tooth appearance of arterial flow in one direction and continuous umbilical venous blood flow in the other. With a pulsed wave Doppler system, an ultrasound scan is first carried out, a free-floating portion of the cord is identified and the Doppler sample volume is placed over an artery and the vein (Figure 4). Normal Pregnancy Development of the umbilcal artery Normal impedance to flow in the umbilical arteries and normal pattern of pulsatility at the umbilical vein in 1 trimester Normal impedance to flow in the umbilical arteries and umbilical vein in early 2trimester Normal impedance to flow in the umbilical arteries and umbilcal vein in late 2 and 3 trimester the location of the Doppler sampling site in the umbilical cord affects the Doppler waveform and the impedance indices are significantly higher at the fetal end of the cord than at the placental end. A possible explanation for this finding is that the fetal placental vascular bed is a low impedance system associated with minimal wave reflection, which explains the presence of continuing forward flow in the umbilical artery during diastole. The closer the measurement site is to the placenta, the less is the wave reflection and the greater the end-diastolic flow. Consequently, the Doppler waveform that represents arterial flow velocity demonstrates progressively declining pulsatility and the indices of pulsatility from the fetal to the placental end of the cord13. Figure 4a: Ultrasound image with color Doppler showing the umbilical cord, red umbilical artery and blue umbilical vein (left). Normal flow velocity waveforms from the umbilical vein (bottom) and artery (top) at 32 weeks of gestation (right). Figure 4b: Normal flow velocity waveforms from the umbilical vein (top) and artery (bottom) at 32 weeks of gestation. There are no appreciable diurnal changes or significant day-to-day variations in pregnancies with normal umbilical arterial Doppler waveforms. Umbilical venous blood flow increases with fetal inspiration (during which the fetal abdominal wall moves inward) and decreases with expiration (during which the wall moves outward). There is also a breathing-related modulation of arterial pulsatility, and umbilical artery Doppler studies should be avoided during fetal breathing. Maternal exercise may cause an increase in fetal heart rate but mild to moderate exercise does not affect flow impedance in the umbilical artery. Umbilical arterial flow waveforms are not affected by fetal behavioral states (sleep or wakefulness). Although, in certain pregnancy disorders (such as pre-eclampsia), fetal blood viscosity is increased, the contribution to the increased impedance in the umbilical artery from viscosity is minimal compared to the coexisting placental pathology. Therefore, the viscosity of fetal blood need not be considered when interpreting the umbilical Doppler indices. With advancing gestation, umbilical arterial Doppler waveforms demonstrate a progressive rise in the end-diastolic velocity and a decrease in the impedance indices (Figure 5). When the high-pass filter is either turned off or set at the lowest value, end-diastolic frequencies may be detected from as early as 10 weeks and in normal pregnancies they are always present from 15 weeks. Human placental studies have demonstrated that there is continuing expansion of the fetoplacental vascular system throughout the pregnancy. Furthermore, the villous vascular system undergoes a transformation, resulting in the appearance of sinusoidal dilatation in the terminal villous capillaries as pregnancy approaches term, and more than 50% of the stromal volume may be vascularized. The intra and interobserver variations in the various indices are about 5% and 10%, respectively 14. Figure 5: Pulsatility index in the umbilical artery with gestation (mean, 95th and 5th centiles). It may be difficult to obtain a low angle because the aorta runs anterior to the fetal spine and, therefore, parallel to the surface of the maternal abdomen. This problem can be overcome, by moving the transducer either toward the fetal head or toward its breech and then tilting the transducer. Flow velocity waveforms in the descending aorta represent the summation of blood flows to and resistance to flow in the kidneys, other abdominal organs, femoral arteries (lower limbs) and placenta. Approximately 50% of blood flow in the descending thoracic aorta is distributed to the umbilical artery. The mean blood velocity increases with gestation up to 32 weeks and then remains constant up to 40 weeks, when there is a small fall (Figure 7) 15. Figure 6: Parasagittal view of the fetal trunk with superimposed color Doppler showing the descending aorta (left). Flow velocity waveforms from the fetal descending aorta at 32 weeks of gestation demonstrating positive end-diastolic velocities (right). Normal Pregnancy Development of the Descending Aorta Color Doppler energy with visualization of the aortic arch and descending thoracic aorta Normal flow of the descending thoracic aorta in 2 and 3 trimesters Figure 7: Pulsatility index (left) and mean blood velocity (right) in the fetal aorta with gestation (mean, 95th and 5th centiles). Renal Artery Color Doppler allows easy identification in a longitudinal view of the fetal renal artery from its origin as a lateral branch of the abdominal aorta to the hilus of the kidney (Figure 8). Diastolic velocities may be physiologically absent until 34 weeks, and then increase significantly with advancing gestation. This may offer an explanation for the increase of fetal urine production that occurs with advancing gestation 18. Figure 8a: Parasagittal view of the fetal trunk with Power Color Doppler showing the renal artery originating from the descending aorta (left). Flow velocity waveforms from the renal artery and vein at 32 weeks of gestation with physiologically absent end-diastolic velocities (right). Figure 8b: Flow velocity waveforms from the renal artery and vein at 32 weeks of gestation with physiologically absent end-diastolic velocities (right). Cerebral Arteries With the color Doppler technique, it is possible to investigate the main cerebral arteries such as the internal carotid artery, the middle cerebral artery, and the anterior and the posterior cerebral arteries and to evaluate the vascular resistances in different areas supplied by these vessels. A transverse view of the fetal brain is obtained at the level of the biparietal diameter. The transducer is then moved towards the base of the skull at the level of the lesser wing of the sphenoid bone.

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Other associated symptoms that may be present the frontal eye feld causes a conjugate deviation of the are transient diplopia, ataxia, vertigo, dysarthria, perioral eyes away from the side of the lesion as an irritative phe paraesthesia, dysphasia, hemiparesis or hemisensory loss. These deviations episodes of falling to the ground without warning or loss of are generally only observed in unconscious patients. However, the eyes are completely normal A haemorrhage in the internal capsule produces a con on examination. The side, and a palsy of horizontal conjugate gaze to the side of word hemicrania was, with the passage of time, corrupted the lesion. In addition to vertigo, dysphagia, signs of cer 50 years, attention has been focused on the concept that ebellar defciency and sensory disturbances due to trigemi migraine is analogous to epilepsy and that clinically appar nal involvement, there is nystagmus and Horner syndrome ent circulating phenomena are actually secondary to neuro (miosis, enophthalmos and ptosis) on the affected side. The frst is brainstem generation, the Cortical Blindness second vasomotor activation in which arteries, both within Aetiopathogenesis: the most common cause is bilateral and outside the brain, may constrict or dilate, and the third occipital lobe infarction. Unilateral infarction leads to is activation of cells of the trigeminal nucleus caudalis contralateral homonymous congruous hemianopia. Activation of any one of these phases artery), and the posterior communicating artery (a branch is suffcient for the production of headache and one phase of the internal carotid artery system). Bilateral occipital may appear to dominate in a particular migrainous syn infarcts result in cortical blindness characterized by its drome. Head injury is the second most as being mainly responsible for triggering the neural origin common cause of Anton syndrome. Migraine has been postulated to represent a is a neoplasm involving the occipital cortex which could be hereditary perturbation of serotonergic neurotransmission. Clinical features: Migraine affects nearly 10% of the Clinical features: Vision and visual felds are markedly population and is characterized by headache, but has been decreased in both eyes when there is bilateral involvement, classifed into various subtypes according to the constella usually with sparing of the macula, but sometimes there tion of symptoms seen (Table 31. When unilateral, in the majority of is contralateral congruous homonymous hemianopia. Patients with stroke may recover vision partially or There may be a past history of car sickness or cyclical vom completely. The episodes may start Giant Cell Arteritis after awakening and are generally relieved by sleep. The symptoms of migraine have been observed to have certain known associations or precipitating factors which Migraine include menstrual cycles, puberty, birth-control or hormonal this is a periodic, typically unilateral, throbbing or boring pills, foods containing tyramine or phenylalanine (such headache accompanied by nausea, vomiting, mood changes, as vintage cheeses, wines, chocolates, cashew nuts), nitrates fatigue and visual disturbances. May have focal neurological disturbances debated without headache or vomiting and are referred to as migraine equivalents or accompani ments. Complicated migraine Migraine with dramatic focal neurological features, thus overlapping with classic migraine, but in the latter the symptoms precede the headache while in complicated migraine they occur at the peak of the headache and persist longer. The term connotes a persisting neurological defcit that is a residuum of a migraine attack or when the neurological defcit outlasts the headache excess of sleep, emotional stress or bright lights. The dura majority of unilateral migraine headaches do, at some tion of each attack varies from 6 hours to 2 days. In migrain point, change sides, so patients who always develop a head ous women, the attacks are known to stop during pregnancy ache on the same side of the head may have a more serious after the second trimester. Secondly, one should pay close at months to a year, and become less frequent and less severe tention to the temporal sequence of symptoms. Patients may experience photophobia during the careful ocular examination including refraction and neuro headache phase. Other neurological defcits such as hemi logical examination, preferably by a neurophysician. Focal motor deficits, speech dis symptoms persisting after the onset of the headache or order, paraesthesiae of the extremities, face, tongue or appearing after the headache phase and (ii) complicated lips and even hemiplegia with total paralysis or weak migraine. Appropriate spectacles should be prescribed extraocular muscles usually occurs as the migrainous for any refractive error. Generalized nondescript band-like discomfort present continuously Cluster headache Unilateral, periorbital, frontal or temporal headache with ipsilateral epiphora, rhinorrhoea, sweating, nasal stuffness and ptosis. Lasts minutes to hours, recurs once or twice daily for several weeks followed by symptom-free intervals of months to years. In acute meningococcal (epidemic) meningitis papilli this due to a descending infective perineuritis is frequently Meningitis present; rarely papilloedema may develop. If the widely open palpebral aperture, often associated with very brain parenchyma is also affected meningoencephalitis is infrequent blinking. It is due either to a systemic infection with unilateral, is more common than that of the third, although organisms such as meningococci, pneumococci, viruses, divergent strabismus due to the latter cause has been etc. The focus (for example, the paranasal sinuses, middle ear), or pupils vary in size, usually showing miosis in the early from a distant septic focus with haematogenous spread. The stages and mydriasis when coma sets in; loss of reaction clinical presentation can be a fulminant acute infection to light is relatively rare. Metastatic endophthalmitis in which progresses in a few hours, a subacute infection that children is an uncommon complication. The blindness may persist for many weeks is most commonly due to Streptococcus pneumoniae after the other symptoms subside, but sight may be ulti (approximately 50% of cases), Neisseria meningitides mately restored. Chronic basal meningitis sometimes (approximately 25%), group B streptococci and Listeria shows the same feature, but in these cases optic neuritis monocytogenes. The incidence of Haemophilus infuenzae and postneuritic atrophy may occur from secondary hydro induced meningitis has decreased following near universal cephalus and pressure of the distended third ventricle immunization with the H. Viruses causing oedema is usually due to complications such as sinus acute meningitis include enteroviruses (poliovirus), arbo thrombosis or cerebral abscess. Chronic meningitis can be due to partially treated is most frequently involved, the paralysis often causing suppurative meningitis, Mycobacterium tuberculosis, Lyme lagophthalmos. Conjugate deviation of the eyes is not disease among the bacterial pathogens; secondary or uncommon. A primary optic somiasis among protozoal pathogens; cysticercosis due atrophy usually develops bilaterally, with a central scotoma to cysts of Taenia solium, Gnathostoma spinigerum and and irregular contraction of the visual felds, either concen Angiostrongylus spinigerum among helminthic organisms. The differential diagnosis the classic clinical features include fever, headache and from a pituitary tumour is based on negative radiological neck stiffness, which are seen in over 90% of cases. Seizures and features In tuberculous meningitis a moderate degree of papil of raised intracranial pressure may be associated and, in litis is common (about 25%) and is generally bilateral. Neck rigid Miliary tubercles in the choroid, though reported in the ity, which is pathognomonic of meningeal irritation, is earlier literature, are only infrequently reported in several Chapter | 31 Diseases of the Nervous System with Ocular Manifestations 523 large series of tubercular meningitis from India, except early symptom and nystagmus may be present. Not infre followed by parkinsonian tremor (paralysis agitans) and, in quently there is a kinetic (not paralytic) conjugate deviation the later stages, spasmodic conjugate deviation of the eyes of the eyes and head to one side. Intracranial tuberculo occurs, usually upwards (oculogyric crises), accompanied mas manifest ocular signs like any other brain tumour. Oculogyric Antitubercular treatment must be administered with iso crises may be relieved by Benzedrine (up to 30 mg a day). The cerebrospinal fuid shows an increase Other Infections in cells with predominantly polymorphonuclear neutrophils in bacterial and lymphocytic pleocytosis in tubercular, viral A collection of pus in the subdural space (subdural empy and fungal infections.

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Temporary iatrogenic fetal tricuspid valve atresia in a case of twin to twin transfusion syndrome. The two methods are complementary to each other, with color Doppler being used for general assessment of flow in the region of interest and pulsed Doppler for targeted examination of flow in a vessel or across a valve 1-10. In pulsed Doppler ultrasound, the examiner positions a sample volume over the region of interest to obtain flow velocity waveforms as a function of time. This makes it possible to quantify blood flow as peak or time-averaged mean velocities, which allow the calculation of ratios (such as the E/A ratio) or blood volume (such as stroke volume or cardiac output) after measurement of vessel diameter. Color Doppler, which is technically easier to perform, allows a rapid assessment of the hemodynamic situation, but gives only descriptive or semi-quantitative information on blood flow. Color Doppler should be an integral part of the routine examination of a fetal heart because this helps to shorten the scanning time, but also provides improved reliability in diagnosing or excluding abnormalities. Several planes, including the abdominal view, four-chamber view, five-chamber view, the short-axis and the three-vessel view need to be assessed to achieve spatial information on different cardiac chambers and vessels as well as their connections to each other 1,2,4. The difference from two-dimensional scanning is that, with color Doppler, the angle of insonation should be as small as possible for optimal visualization of flow. In the abdominal plane, the position of the aorta, inferior vena cava and the connection of the vein to the right atrium are examined. Pulsed Doppler sampling from the inferior vena cava, the ductus venosus or the hepatic veins can be achieved in longitudinal planes. Using color Doppler in an apical (Figure 1) or basal approach, the diastolic perfusion across the atrioventricular valves can be assessed; there is a characteristic separate perfusion of both inflow tracts during diastole (Figure 1). Using pulsed Doppler, there is a typical biphasic shape of the diastolic flow velocity waveform with an early peak diastolic velocity (E) and a second peak during atrial contraction (A-wave); E is smaller than A, and the E : A ratio increases during pregnancy toward 1, to be inversed after birth. In this plane, regurgitation across the atrioventricular valves, which is more frequent at the tricuspid valve, is easily detected during systole with color Doppler. Flow across the foramen ovale is visualized in a lateral approach of the four-chamber view. Color Doppler allows confirmation of the physiological right-to-left shunt and visualization of the pulmonary veins as they enter the left atrium. The transducer is then tilted to obtain the five-chamber view and then the short-axis view. The aorta, arising from the left ventricle, is seen and color shows the laminar flow across the aortic valve during systole. With pulsed Doppler, a single peak flow velocity waveform for the aortic and pulmonary valves is demonstrated. The peak systolic velocity increases from 50 to 110 cm/s during the second half of pregnancy and is higher across the aortic than the pulmonary valve. The three-vessel view enables assessment of the aortic arch and the ductus arteriosus. In the third trimester, an aliased flow is found within the ductus as a sign of the onset of constriction. When the fetal position is optimal, the aortic arch and ductus arteriosus can be seen in a longitudinal plane, allowing visualization of neck vessels. Figure 7: Three-dimensional power Doppler ultrasound of the crossing of the great vessels in a 28-week fetus. In the four chamber view, the right ventricle is hypoplastic or absent and color Doppler demonstrates the absence of flow from the right atrium to the right ventricle (Figure 3). Blood from the right atrium flows across the foramen ovale to the left atrium and from there during diastole to the left ventricle. This unilateral perfusion across the left ventricular inflow tract is typical for this lesion. In the presence of an associated ventricular septal defect, a left-to-right shunt into the small right ventricular cavity is found. Figure 9: the right ventricle is hypoplastic or absent and color Doppler demonstrates the absence or minimum flow from the right atrium to the right ventricle. Tricuspid dysplasia and Ebstein anomaly In tricuspid dysplasia, the valve leaflets are correctly inserted but they are thickened. By contrast, the valve leaflets in Ebstein anomaly are inserted abnormally so that they are more apical in the right ventricle and their ability to close is reduced. In both conditions there is tricuspid regurgitation which is generally associated with dilatation of the right atrium and, in extreme forms, with gross cardiomegaly (Figure 4) 11,12. Color Doppler is used to confirm tricuspid regurgitation and spectral Doppler (Figure 5) is used to measure the pressure gradient and duration of the regurgitation. Since both anomalies are associated with an obstruction of the right ventricular outflow tract (pulmonary stenosis or atresia), it is mandatory to analyze the perfusion in the pulmonary trunk. In severe obstruction, retrograde flow within the ductus arteriosus is found (see Figure 6). This, however, does not prove pulmonary atresia because a patent but stenotic pulmonary valve, due to tricuspid regurgitation, can show the same features as an atresia and thus leads to a false-positive result 12. Figure 10: the characteristic finding is that of a massively enlarged right atrium, a small right ventricle, and a small pulmonary artery. Doppler can be used to demonstrate regurgitation in the right atrium Pulmonary atresia and intact ventricular septum this diagnosis includes a group of heart defects with an atretic pulmonary valve and an intact ventricular septum. The size and shape of the right ventricle show a wide range, from hypoplastic to normal sized or even dilated. In both former types, the right ventricle shows no contractility and the tricuspid valve movements are reduced. Color Doppler in the four-chamber view shows absence or reduced tricuspid flow and, during systole, there may be tricuspid valve regurgitation. In the three-vessel view or the short-axis view, there is absence of antegrade perfusion across the pulmonary valve and retrograde flow through the ductus arteriosus (Figure 6). The pulmonary trunk in these conditions is narrower than the ascending aorta, but is not severely hypoplastic because of retrograde perfusion through the ductus arteriosus. In some hearts with pulmonary atresia, communications between the hypoplastic right ventricle and the coronary arteries may be present and are detectable by color Doppler ultrasound 13 in mid-gestation. Figure 11: Tricuspid valve dysplasia with severe tricuspid insufficiency and cardiomegaly. Pulsed wave Doppler (left) is not useful due to the aliasing phenomenon and the maximal velocities that can be assessed are 180 cm/s (arrow). The continuous wave transducer allows assessment of very high velocities; in this case 420 cm/s Figure 13: Hypoplastic right ventricle (arrow) in a fetus with pulmonary atresia and intact ventricular septum (a). Color doppler of the 4 chamber view with asymmetric flow between the left heart and right heart. Pulmonary stenosis In the isolated form of this lesion, there is narrowing of the semilunar valves. In severe cases, a hypokinetic and hypertrophied right ventricle can be found but most cases are not detected prenatally. On two-dimensional imaging, the diagnosis is suspected by the presence of poststenotic dilatation of the pulmonary trunk and reduction of pulmonary valve excursion. With color Doppler, the diagnosis is easy and is based on the demonstration of turbulent flow across the pulmonary valve. Doppler flow velocity waveforms using a continuous wave transducer enable the demonstration of high velocities (more than 2 m/s), which are typical of stenosis. These findings, either in color or in pulsed Doppler, are only typical of the isolated form and are not commonly found in conditions associated with a ventricular septal defect, such as tetralogy of Fallot or double outlet right ventricle. Fetal pulmonary stenosis can be associated in the third trimester with tricuspid insufficiency, leading in some cases to right atrial dilatation 8. Aortic stenosis In general, the narrowing is found at the level of the aortic valve and a simple stenosis is rarely detected in the four chamber view.

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Nystagmus is noticeable and cosmetically disturbing except when excursions of the eye are very small. End-Point (End-Gaze) Nystagmus Normal individuals may have nystagmus on extreme horizontal gaze, which disappears when the eyes are moved centrally by a few degrees. It is primarily horizontal but may have a slight torsional component and greater amplitude in the abducting eye. Optokinetic Nystagmus this type of nystagmus may be elicited in all normal individuals, usually with a rotating drum with alternating black and white lines but by any repetitive targets in the visual field, such as repetitive telephone poles as seen from a window of a fast-moving vehicle. The slow component follows the object, and the fast component moves rapidly in the opposite direction to fixate on the succeeding object. A unilateral or asymmetric horizontal response usually indicates a deep parietal lobe lesion, especially a tumor. Anterior cerebral (ie, frontal lobe) lesions may inhibit this response only temporarily when an acute saccadic gaze palsy is present, which suggests the presence of a compensatory mechanism that is much greater than for lesions situated farther posteriorly. Since it is an involuntary response, this test is especially useful in detecting functional visual loss. Stimulation of Semicircular Canals the three semicircular canals of each inner ear sense movements of the head in space, being primarily sensitive to acceleration. The neural output of the vestibular system, after processing within the vestibular and related brainstem nuclei, is a velocity signal. In the unconscious subject with an intact brainstem, this leads to a tonic deviation of the eyes, whereas in the conscious subject, a superimposed corrective fast-phase movement, returning the eyes back toward the straight ahead position, results in a jerk nystagmus. These tests are useful methods of investigating vestibular function in conscious subjects and, in the case of caloric stimulation, brainstem function in comatose patients. Rotation, such as in a Barany chair, then leads to horizontal jerk nystagmus with the compensatory slow-phase eye movement opposite to the direction of turning and the corrective fast phase in the direction of turning. Due to impersistence of the vestibular signal during continued rotation, the nystagmus abates. Once the rotation stops, there is a vestibular tone in the opposite direction, which results in a jerk nystagmus with the fast phase away from the original direction of turning (postrotatory nystagmus). Since the 690 subject is stationary, postrotatory nystagmus is often easier to analyze than the nystagmus during rotation. Water irrigation of the auditory canal generates convection currents predominantly within the horizontal rather than the vertical semicircular canals. Cold water irrigation induces a predominantly horizontal jerk nystagmus with a fast phase opposite to the side of irrigation, and warm water irrigation induces a similar jerk nystagmus with a fast phase toward the side of irrigation. It is important to verify that the tympanic membrane is intact before performing irrigation of the external auditory canal. Congenital Nystagmus Congenital nystagmus is nystagmus present within 6 months after birth. Ocular instability is usual at birth, due to poor visual fixation, but this abates during the first few weeks of life. Congenital impairment of vision or visual deprivation due to lesions in any part of the eye or optic nerve can result in nystagmus at birth or soon thereafter. Causes include corneal opacity, cataract, albinism, achromatopsia, bilateral macular disease, aniridia, and optic atrophy. By definition, congenital idiopathic motor nystagmus has no associated underlying sensory abnormality, although visual performance is limited by the ocular instability. Typically it is not present at birth but becomes apparent between 3 and 6 months of age. At one time it was thought that congenital pendular nystagmus was indicative of an underlying sensory abnormality whereas congenital jerk nystagmus was not. Eye movement recordings have shown this not to be true, with both 691 pendular and jerk waveforms being seen whether or not there is a sensory abnormality. Indeed, in many cases, a mixed pattern of alternating pendular and jerk waveforms is seen. Congenital nystagmus, particularly the idiopathic motor type with its potential for better visual fixation, generally undergoes a progressive change in its waveform during early childhood. There is development of periods of relative ocular stability, that is, relatively slow eye velocity, known as foveation periods since they are thought to be an adaptive response to maximize the potential for fixation, and hence to improve visual acuity. In addition, congenital nystagmus with a jerk nystagmus has a characteristic waveform in which the slow phases have an exponentially increasing velocity. This can be a particularly useful feature in determining that nystagmus noted in adulthood is not of recent onset. The direction of any jerk component often varies with the direction of gaze, but an important feature in comparison to many forms of acquired nystagmus is that there is no additional vertical component on vertical gaze. In most patients with congenital nystagmus, there is a direction of gaze (null zone) in which the nystagmus is relatively quiet. If this null zone is away from primary position, a head turn may be adopted to place the eccentric position straight ahead. In a few cases, the position of the null zone varies to produce the congenital type of periodic alternating nystagmus. Congenital nystagmus is usually decreased in intensity by convergence, and some patients will adopt an esotropia (nystagmus blockage). Once congenital nystagmus has been noted, it is important to identify any underlying sensory abnormality, if only to determine the visual potential. Extraocular muscle surgery is predominantly indicated for patients with a marked head turn. Supramaximal recessions of the horizontal rectus muscles reduce the intensity of congenital nystagmus, but the effect is only temporary. Nystagmus with a latent component means that it increases in intensity when one eye is covered, which is a characteristic feature of congenital nystagmus. This may be because of loss of sight in one eye or even from the development of a divergent squint. Acquired Pendular Nystagmus Any child who develops bilateral visual loss before 6 years of age may also develop a pendular nystagmus, and indeed the acquisition of a pendular nystagmus during infancy necessitates further investigation. A specific syndrome of acquired pendular nystagmus in childhood is spasmus nutans. This is a bilateral, generally horizontal (occasionally vertical), fine, dissociated pendular nystagmus, associated with head nodding and an abnormal head posture. There is a benign form, which may be familial, with onset before age 2 and spontaneous improvement during the third or fourth year. Spasmus nutans may also rarely be the first manifestation of an anterior visual pathway glioma. In adults, acquired pendular nystagmus is a feature of brainstem disease, usually multiple sclerosis or brainstem stroke. There may be horizontal, vertical, or torsional components or even a combination of components to produce oblique or elliptical trajectories. The syndrome of oculopalatal myoclonus characteristically develops several months after a brainstem stroke. There is pendular nystagmus with synchronous movements variably involving the soft palate, larynx, and diaphragm as well as producing head titubation. Various drug treatments have been tried for adult acquired pendular nystagmus, of which gabapentin, memantine, and baclofen have produced the best, although still limited, results. Vestibular Nystagmus Abnormalities of vestibular tone result in abnormal activation of the vestibulo ocular pathways and abnormal neural drive to the extraocular muscles. Loss of function in the left horizontal semicircular canal is equivalent to activation of the right horizontal semicircular canal, as would normally be produced by a rightward head turn. The corrective fast-phase response is rightward in direction, and a right-beating horizontal nystagmus is thus generated. The pattern of response to dysfunction of one or more semicircular canals can be similarly derived to give the full possible range of peripheral vestibular nystagmus, although in clinical practice, it is the effect of dysfunction of the horizontal canals that usually predominates. As a general rule, peripheral vestibular lesions are destructive, and the fast phase of the resulting nystagmus is away from the side of the lesion. Since the neural signal of the vestibulo-ocular pathways is a velocity signal, the slow phase of peripheral vestibular nystagmus has a constant velocity.

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Many of these stain poorly, showing that they are In some cases, lesions of the fundus resemble retinal or undergoing necrosis (Fig. When noticed the vitreous may be so involved that details of the retina very early, as may occur in the fellow eye, a larger mass is are obscured. Micro Vitrectomy may provide the only available source for scopically, minute deposits are seen scattered in various tissue diagnosis in ocular reticulum cell sarcoma. It may grow mainly outwards, mour cells are large and pleomorphic with scanty cyto separating the retina from the choroid (glioma exophytum), plasm and prominent nuclear membranes. Nuclei are round or inwards towards the vitreous (glioma endophytum); or oval, occasionally multiple with frequent mitoses, there is no fundamental distinction between the two, but clumped chromatin and prominent nucleoli. In the former, the the differential diagnosis is from leukaemic infltrates, condition resembles a detachment of the retina; in the latter retinitis secondary to bacterial or fungal sepsis, toxoplas polypoid masses, sometimes with haemorrhages on the mosis and cytomegalovirus infection. The diagnosis is of some importance because radiation therapy is effective and can lead to permanent improvement Clinical Course in visual acuity. Retinoblastoma If left untreated retinoblastoma runs through the same Retinoblastoma is a proliferation of neural cells which stages as melanoma of the choroid: have failed to evolve normally. The glaucomatous stage neuroglia, such as those that occur in the brain and optic 3. The stage of extraocular extension and nerve, are very rare in the retina and it is better termed 4. The second stage results in enlargement of the globe, Aetiology with apparent or real proptosis. Pain is severe during this the tumour is confned to infants and very young children stage, but is relieved when the tumour bursts through and is frequently congenital, although it may remain quies the sclera, an event that usually occurs at the limbus and is cent or pass unnoticed until the ffth or sixth year of life or followed by rapid fungation. The fellow eye is preauricular and neighbouring lymph nodes, later in the affected independently, not by metastasis, in about one cranial and other bones. However, frequently the growth cannot the optic nerve (which is affected early) and brain is more be recognized, even on careful examination, until months or common, while metastases in other organs, usually the even years later. Clinically a caulifower-like mass had a retinoblastoma, and in such cases the disease is arising from the retina is seen extending into the vitreous usually, but not always, bilateral. There is neovascularization on same family are sometimes affected as the inheritance is the surface with white areas of calcifcation. This chromosome is responsible for control esotropia is sometimes the presenting clinical picture. This classifcation was used to predict which ease-free survival in intraocular retinoblastoma is more eyes were likely to survive local therapy and keep useful than 90%. The International Classifcation of Retinoblastoma was devised in 1990, to refect changing paradigms in therapy, Group I. Highly unfavourable for maintenance of sight: sure should be recorded, as it is raised more often seen in l Massive tumours involving more than one half the retinoblastoma, whereas lowered intraocular pressure is retina common in pseudoglioma. Diagnosis Improved diagnostic techniques, including the indirect Calcifcation occurs in 75% of cases and is almost pathog ophthalmoscope and new treatment options, underline the nomonic of retinoblastoma. B-scan ultrasonography displays a cauli seeding is now frequently treated successfully with fower-like mass arising from the retina, with or without a brachytherapy. Even when every precaution is taken, in some cases it is impossible to be certain of the diagnosis. Considering that the life of the patient is at stake, if the eye is rendered useless as an organ of sight, these should be treated as malignant. Radioactive cobalt discs sutured to the sclera over the site of the nodule are employed to can also be visualized. The isotope125 I is increasingly being tissue is echo dense giving rise to high spikes and areas used and the plaques are custom-built for each child. Late of necrosis within the mass return spikes of lower ampli sequelae of irradiation are thin greyish exudates at the tude. Extension of the disease to the conjunctiva or orbital or younger and 560 to 600 mg/m2 for older children), and tissues warrant exenteration of the orbit. External beam etoposide (5 mg/kg for children 36 months or younger and radiation therapy was an alternative to enucleation. Metastatic deposits from tumours in other parts of the the prognosis of retinoblastoma, if untreated, is always body are usually from primary malignancies of the breast, bad, and the patient invariably dies. Success with chemore lung, gastrointestinal tract, kidneys, prostate, thyroid duction for retinoblastoma, defned as avoidance of exter and testes and are most commonly located in the choroid, nal-beam radiation and enucleation, was 100% for group A, but can also be seen in the iris. The metastatic tumours 93% for group B, 90% for group C and 47% for group D in are, however, radiosensitive so they do respond to local the International Classifcation. Online multimedia database endorsed by the International Council of Ophthalmology. The David G Cogan Ophthalmic Pathology Collection: A tumours arise from the uveal tract or retina. Retinoblastoma study and teaching collection of clinical ophthalmic cases and their is the commonest intraocular malignancy in children pathology. Chapter 24 Injuries to the Eye Chapter Outline Chemical Injuries 383 Wounds of the Conjunctiva 393 Alkalis 383 Wounds of the Cornea and Sclera 393 Acids 384 Wounds of the Lens 393 Mechanical Injuries 384 Open Globe Penetrating Wounds with the Retention of Foreign Superfcial Foreign Bodies 385 Bodies 394 Closed Globe, Concussion or Contusion Injury 386 Mechanical Effects 394 Cornea 387 Infection 395 Sclera 388 Reaction of the Ocular Tissues to a Foreign Body 395 Iris and Ciliary Body 388 Diagnosis 396 Lens 389 Treatment 397 Vitreous 391 Sympathetic Ophthalmitis 397 Choroid 392 Aetiology 398 Retina 392 Pathology 398 Optic Nerve 392 Clinical Features 398 Intraocular Pressure 392 Treatment 398 Open Globe Penetrating Injuries 392 the eye is protected from direct injury by the lids, eye Immediately after the accident there is intense conjuncti lashes and the projecting margins of the orbit. Nevertheless, vitis and chemosis, but the cornea often looks clear, and it is therefore diffcult to ascertain the severity of the injury. Prognosis should therefore be guarded, care being taken Alkalis to impress upon the patient the gravity of the injury and Injuries by caustics such as lime usually occur from fresh the necessity for supervision. In the worst cases, the cornea mortar or whitewash entering the eye or from laboratory is dull or opaque. The cell membranes, destroying collagen and proteoglycans in corneal changes should be treated as an ulcer. These may cause considerable damage to the lime burns the entire cornea may be destroyed, perforation eye because they penetrate and cause necrosis of the sur takes place and the eye shrinks. In less severe cases a por face epithelium in a few seconds with occlusion of the celain-like, dense, vascularized leucoma forms and sight limbal vasculature. The chief danger resulting from the condition of of the anterior segment, corneal opacifcation and melting, the conjunctiva is damage to the ocular surface, with severe cataract and symblepharon. It is most ide are particularly harmful, as they cause necrosis of the likely to occur in the lower lid where the lower fornix is cornea. Corticosteroids are potent agents in reducing the in fammatory reaction and prevent the formation of exces sive granulation tissue, which determines the development of symblepharon. They can be used topically as drops or ointment for the frst 10 days, together with acetazol amide tablets to lower the intraocular pressure. Thereafter, steroids are stopped as they impair healing and may pre cipitate corneal melting. Ascorbic acid and tetracyclines are given topically and systemically to enhance collagen formation. To inhibit collagenolysis and stromal damage, 10% sodium citrate, 5% N-acetylcysteine or 1% medroxy progesterone eye drops are useful adjuncts. The ftting of a contact lens sepa Chemical Burns rates the two mucosal surfaces and prevents their adhesion. Epithelial Perilimbal Revascularization of the limbus and re-epithelialization Grade Damage Stroma Ischaemia Prognosis of the ocular surface can be stimulated by a limbal cell transplant or amniotic membrane graft. They should also be treated by copious irriga tion with normal saline or any clean fuid at hand. Limbal Trauma Classifcation Group has attempted to develop a ischaemia leads to severe damage of the limbal stem cells.

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The pulsatility indices in the uterine and umbilical arteries and in the fetal middle cerebral arteries and thoracic aorta are not significantly different from normal and there are no significant differences between these values in those with and without intrauterine infection. Thus, in fetuses that subsequently develop pulmonary hypoplasia, impedance in the peripheralpulmonary arteries is increased from as early as 2 weeks after amniorrhexis. Preterm prelabour amniorrhexis: intrauterine infection and interval between membrane rupture and delivery. Concentration of fetal plasma and amniotic fluid interleukin-1 in pregnancies complicated by preterm prelabour amniorrhexis. Doppler studies of the placental and fetal circulation in pregnancies with preterm prelabour amniorrhexis. Pressor and depressor actions of prostanoids in the intact human feto-placental vascular bed. Effects of vasoactive autocoids on the human umbilical-fetal placental vasculature. A model of bacterially induced umbilical vein spasm, relevant to fetal hypoperfusion. Fetoplacental and uteroplacental Doppler blood flow velocity analysis in premature rupture of membranes. Assessment of fetal activity and amniotic fluid volume in the prediction of intrauterine infection in preterm prelabor amniorrhexis. Ductus arteriosus flow velocity modulation by fetal breathing movements as a measure of fetal lung development. Doppler ultrasound imaging: a new technique to detect lung hypoplasia before birth In pregnant women with systemic lupus erythematosus, the rate of fetal loss in the first trimester is similar to that in normal women (about 15%), but, in the second and third trimesters, the fetal loss rate is about 10%1,2. The mechanism for this increase in fetal loss is unclear but may be related to placental dysfunction. About 25% of pregnancies in women with systemic lupus erythematosus are complicated by pre-eclampsia 3. The reason for this increased frequency of pre-eclampsia may be related to the underlying renal disease 6. Distinguishing between an exacerbation of systemic lupus erythematosus involving active nephritis and pre-eclampsia is difficult, since they may both present with proteinuria, hypertension and evidence of multi-organ dysfunction. In the typical problem case, the patient develops hypertension and increasing proteinuria in the latter half of pregnancy. In severe and confusing cases, renal biopsy may be necessary to make the correct diagnosis. Neonatal lupus erythematosus, with a birth prevalence of about one in 20 000, is characterized by dermatological, cardiac or hematological abnormalities. About half of the mothers who deliver an infant with neonatal lupus erythematosus have systemic lupus erythematosus or another autoimmune disease. The cardiac lesions associated with the condition are congenital complete heart block and endocardial fibroelastosis. The histological lesion is one of fibrosis and interruption of the conduction system, especially in the area of the atrioventricular node. Because the lesion is permanent, a pacemaker may be necessary for neonatal survival. After prenatal diagnosis of fetal heart block, administration of a glucocorticoid to the mother is associated with improvement in fetal cardiac function and limitation of further immunological damage to the fetal heart 9,10. The risk of thrombosis in pregnancy in women with antiphospholipid syndrome is sufficiently substantial to warrant prophylactic treatment with heparin. Antiphospholipid syndrome is associated with early pregnancy loss; antiphospholipid antibodies are found in about 10% of women with recurrent first-trimester pregnancy loss (compared to about 2. About 50% of women with antiphospholipid syndrome develop pre-eclampsia, which may start from as early as 15 weeks, or worsening hypertension 16,17 and about 10% of women with severe earlyonset (before 34 weeks) pre-eclampsia have antiphospholipid antibodies. The rate of pre-eclampsia does not appear to be markedly diminished by treatment with either glucocorticoids with low-dose aspirin or heparin with low-dose aspirin. The syndrome is also associated with fetal growth impairment, which is found in about 30% of treated pregnancies 16,17. They reported that the absence of end-diastolic frequencies in the umbilical artery was a good predictor of the need for subsequent delivery by Cesarean section, whereas the presence of end-diastolic frequencies was associated with normotensive pregnancy 22. In systemic lupus erythematosus, it is uncertain if impedance to flow in the uterine arteries is increased. Impedance to flow in the uterine artery was within the normal range in all cases, whereas most values from the umbilical artery were above the 95th centile of the normal range. All five pregnancies resulted in healthy live births but one infant was growth-restricted; the highest impedance in the umbilical artery was observed in the case of growth restriction. In 18 pregnancies, there was normal impedance in both the uterine and umbilical arteries and they all had normal outcomes. In five pregnancies, there was normal impedance in the uterine arteries but increased impedance in the umbilical artery and, in this group, there were two cases of intrauterine growth restriction. In four pregnancies, there was increased impedance in both vessels; in all four, there was intrauterine growth restriction and three resulted in intrauterine or neonatal death. In antiphospholipid syndrome there is thrombosis of the uteroplacental vasculature and placental infarction. There is some evidence that, in pregnancies with antiphospholipid syndrome, increased impedance in the uterine arteries identifies those cases that subsequently develop pre-eclampsia and intrauterine growth restriction. In this respect, the findings of Doppler studies in predicting the outcome of pregnancies with the antiphospholipid syndrome may be similar to those with placental insufficiency due to impaired trophoblastic invasion of the maternal spiral arteries. They examined six pregnancies in women with antiphospholipid syndrome and reported increased impedance to flow in the umbilical artery in four of the cases, despite the absence of pre-eclampsia or intrauterine growth restriction. Further evidence emphasizing the difference in the implications of antiphospholipid syndrome from impaired trophoblastic invasion was provided by the studies of Carroll 28. He examined 28 pregnancies complicated by antiphospholipid syndrome and reported that, in five of the six cases associated with intrauterine growth restriction, impedance to flow in the umbilical arteries was increased, whereas only two of these patients demonstrated abnormally elevated impedance in the uterine arteries. Effects of vasoactive autocoids on different segments of human umbilicoplacental vessels. Relationship of systolic/diastolic ratios from umbilical velocimetry to fetal heart rate. Clinical chorioamnionitis is not predicted by umbilical artery doppler velocimetry in patients with premature rupture of membranes. The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in preterm premature rupture of the membranes. The ultrasonographic assessment of the fetal thorax and fetal breathing movements in the prediction of pulmonary hypoplasia. Direct ultrasonographic measurement of fetal lung length in normal pregnancies and pregnancies complicated by prolonged rupture of membranes. Fetal breathing movements are not a reliable predictor of continued lung development in pregnancies complicated by oligohydramnios. Predicting pulmonary hypoplasia: assessment of lung volume or lung function or both Doppler waveforms from the pulmonary arterial system in normal fetuses and those with pulmonary hypoplasia. Oshimura S, Masuzaki H, Miura K, Muta K, Gotoh H, Ishimaru T Diagnosis of fetal pulmonary hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler ultrasonography. Blood flow velocity waveforms from fetal peripheral pulmonary arteries in pregnancies with preterm premature rupture of membranes: relationship with pulmonary hypoplasia. In about 30% of post-term pregnancies, the fetuses develop a postmaturity syndrome, characterized by growth restriction, dehydration, severe desquamation of the epidermis, bile-stained nails and amnion, advanced hardness of the skull, absence of the vernix caseosa and lanugo hair.

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