By P. Rune. South Dakota School of Mines and Technology.

By repeated testing of the antiseizure efect of phenytoin in large However purchase viagra with dapoxetine 100/60 mg, there is agreement that drug resistance is a graded pro- groups of fully kindled rats buy viagra with dapoxetine 100/60 mg fast delivery, we found that the individual response cess generic 100/60 mg viagra with dapoxetine with amex, and past treatment history does have some bearing on future of such rats to phenytoin difers; that is, that kindled seizures in response. Although relative drug resistance can be identifed afer some animals consistently respond and others never respond to failure of two past drugs [11], a signifcant minority of patients phenytoin [7]. For example, the use of carbamazepine in a patient with ab- nobarbital at maximal tolerated doses resulted in two subgroups: sence seizures and generalized spike–wave activity can exacerbate responders and non-responders [7]. Similarly, treating a patient with complex partial seizures phenobarbital non-responders, which was confrmed by several with ethosuximide is unlikely to be efcacious. When the as gabapentin, pregabalin, vigabatrin and lamotrigine can exacer- phenobarbital-resistant rats were subsequently treated with pheny- bate myoclonic seizures [1,14]. Plasma drug levels and adverse efects of [1,14], nor are mechanisms of comorbidity or mortality associated phenobarbital and phenytoin were comparable in responders and with drug resistance. Most of the poten- The underlying epilepsy syndrome is a signifcant predictor for tial mechanisms illustrated in Figure 7. Clinical features such as the epilepsy syndrome or the aeti- and a role for genetic factors (Figure 7. However, in some epileptic syndromes, the proportion of pa- tients with drug-resistant epilepsy varies considerably and the de- Disease-related mechanisms of drug terminants of this variation are largely unknown [1]. Schramm [28] noted that ly, similar observations were made in the rat model of basolateral class I evidence relating seizure outcome to the type and extent of amygdala stimulation that allows diferentiation of rats with difer- resection of mesial temporal lobe structures was inadequate. Epileptic rats that responded to treatment studies reviewed found no positive correlation between extent of exhibited a relatively low, uniform seizure frequency; none of the mesial resection and seizure-freedom afer surgery, and even leav- responders had a high seizure frequency. In contrast, many non-re- ing hippocampus and amygdala untouched could result in sei- sponders exhibited very high seizure frequencies. As in the structures of the mesial temporal lobe are involved in generating clinical situation [21], although high seizure frequency is a reliable or maintaining drug resistance is that the results of seizure free- predictor of pharmacoresistance [20], it is clearly not the only de- dom afer surgery can only be fully attributed to surgery if no pre- terminant of pharmacoresistance. Rogawski [19] mentioned other viously drug-resistant patients become seizure-free without surgery measures of epilepsy severity, such as the extent of structural lesions [27,29]. In a Furthermore, disease-related mechanisms of drug resistance study from Bonn, Germany, the seizure outcome of drug-resistant can change in the course of the epilepsy. Both groups seizure-free having relapsed and 10% had never been seizure-free received medical treatment. In a prospective, long-term, population-based study of 144 seizure-free in the last year of follow-up, as many as 24% of patients patients followed for a median of 40 years since their frst seizure became seizure-free without undergoing surgery, just with a change before the age of 16 years, 19% of patients were drug resistant from of medical regimen [31]. In addition, a number of clinical observa- the start to the end of follow-up, while a further 14% relapsed afer tions have reported that around 20% of formerly drug-resistant pa- remission and became drug resistant, indicating a worsening course tients with partial epilepsy, including patients ineligible for surgery, of epilepsy [22]. On the other hand, 32% of patients became sei- become seizure-free without surgery through a change of medical zure-free afer a median of 9 years of unsuccessful treatment and regimen [32,33,34]. Tese fndings have important implications in the search for This longitudinal study provided incontrovertible evidence that structural brain alterations associated with drug resistance. Tere is preliminary evidence from its underlying mechanisms must have changed over time. Seizures functional imaging [35,36] and from transcranial magnetic stimu- have been postulated to be, among other non-seizure-related fac- lation for changes in the contralateral hemisphere afer successful tors, involved in the generation of drug resistance. Extended changes in excitability and tion is supported by the observation that seizure clusters, defned in functional imaging afer surgery may be related to widespread as three or more seizures in 24 hours, occurring ofen as long as functional impairment in patients with partial epilepsy and sup- 15 years afer starting drug treatment, increased the risk of having port the existence of network changes beyond the resected area drug-resistant epilepsy by a factor of three compared with those in patients undergoing temporal lobe surgery. The network hypothesis of drug resistance afer surgery is based on the existence of non-resected limbic or extralimbic seizure-gen- Structural brain alterations and/or network changes erators lef behind during surgery. In experimental models of epilepsy tered in neocortical neurons from the same patients, and only half this has been called ‘rewiring the brain’ [42]. Indeed, loss of neurons in the hilus of the dentate gyrus, which macoresistant patients, whereas recovery was markedly slowed in is closely associated with development of granule cell disinhibition cells from carbamazepine-responsive patients [50]. The response to prolonged covery from inactivation of Na+ channels of hippocampal granule daily administration of phenobarbital at maximum tolerable doses neurons were signifcantly reduced, although not as pronounced as in epileptic rats of this model can be divided into two categories: a observed with carbamazepine, substantiating the concept that re- responder subgroup with control of seizures and a non-responder duced pharmacosensitivity of Na+ channels may contribute to the subgroup without any signifcant reduction in seizure frequency. This progressive development of pharmacore- correlated with profound alterations in receptor function and phar- sistance during a sustained status epilepticus is paralleled by alter- macology [57,58,59]. Tey found that: tumours, infectious diseases and several brain disorders[70,71,73]. Furthermore, P-gp is ex- sistant epileptic cases but not in drug-sensitive patients or postmor- pressed by tissues with excretory function (small intestine, liver and tem controls. Terefore the development of strategies for bypass- illary endothelial cells, astroglia and neurons following seizures (cf. This could explain that one of the major of inhibitors for the transporters has become an imperative for the predictors of drug resistance is high seizure frequency (or density) pharmaceutical industry [75]. Following the report by necessarily be restricted to the brain, but could also occur in other Tishler et al. If drug resistance is due to such processes, it should be pos- Mdr1 knockout mice were also used to demonstrate P-gp transport sible to demonstrate that the inhibition or avoidance of the of carbamazepine [85] and topiramate [86]. By using a rat microdi- resistance-mediating mechanism counteracts drug resistance in ep- alysis model with microdialysis probes in both brain hemispheres ilepsy. However, have an increased expression of P-gp in focal epileptiogenic brain subsequent data from our group demonstrated species diferenc- tissue. The only could be demonstrated with rodent but not human P-gp in an in exception was levetiracetam which was as efcacious in both re- vitro transport assay [87]. For this purpose, we used epileptic modify such assays in a way that allows evaluating active transport rats that were either responsive or resistant to phenobarbital [99]. A similar clinical tially identifed as substrates of human Pgp by our group, oxcarba- efect of verapamil was reported by Iannetti et al. However, zepine, eslicarbazepine acetate and the carbamazepine metabolite such anecdotes are weak evidence. Tus, clinical trials with more carbamazepine-10,11-epoxide are transported by human P-gp. One major reason for inconsistent data on this pol- develops to some drug efects much more rapidly than to others. Because of diverse confounding 2 have appropriate functionality; factors, detecting tolerance in patients with epilepsy is more dif- 3 be active in drug resistance (and not be an epiphenomenon); and cult but can be achieved with careful assessment of decline during 4 drug resistance should be afected when the mechanism is over- long-term individual patient response. We resistance in epilepsy did not include tolerance as a resistance mechanism in Table 7. For data on the hypotheses see the present and previous reviews [1,4,10,19,47,71]. New avenues for antiepileptic both mechanisms of refractoriness may coexist in the same epilep- drug discovery and development. N Engl J Med 2000; with epilepsy may be a consequence of the disease, the treatment, 342: 314–319. Quantifying the response to antiepileptic drugs: efect of past genetic factors or combinations of these possibilities. Long-term seizure outcomes following epi- pocampal sclerosis or cortical dysplasia) and beyond may be in- lepsy surgery: a systematic review and meta-analysis. Epi- severity and long-term progressive changes in neural networks dur- lepsy Behav 2008; 12: 501–539.

Randomized clinical trial of the efcacy of antiepileptic use of generic versus brand-name antiepileptic drugs: a systematic review and me- drugs in reducing the risk of relapse afer frst unprovoked tonic–clonic seizure buy generic viagra with dapoxetine 100/60 mg on line. Prediction of risk of seizure recurrence the urban community of Nouakchott (Mauritania) discount viagra with dapoxetine online. Quality of life outcomes of immediate or therapy for prehospital status epilepticus purchase viagra with dapoxetine 100/60mg on line. Practice parameter: long-term treatment of the child tability for carbamazepine, phenytoin and phenobarbital or primidone in mono- with simple febrile seizures. Prediction of seizure likelihood with a trolled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68: long-term, implanted seizure advisory system in patients with drug-resistant epi- 402–408. Seizure detection, seizure pre- cohort of consecutive patients with drug-refractory epilepsy. Terapeutic safety monitoring: what to look for and when to look for therapy based on mechanisms of action: the evidence reviewed. The pharmacology of new antiepileptic drugs: does a novel mechanism barbital, phenytoin, and primidone in partial and secondarily generalized tonic– of action really matter? Carbamazepine vs diphenylhydantoin vs their combination in suximide combination therapy for refractory absence seizures. Lamotrigine substitution study: evi- therapy in patients with partial epilepsy failing on a single drug: a multicentre, dence for synergism with sodium valproate. Factors determining response to antie- cation in refractory complex partial seizures: evidence for a pharmacodynamic pileptic drugs in randomized controlled trials: a systematic review and meta-anal- interaction. Seizure-free outcome in randomized add-on data grouped by mechanism of action of concomitant antiepileptic drugs. Withdrawal of antiepileptic drugs: guidelines eral features and interactions between antiepileptic drugs. Curr fects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large Opin Neurol 2014; 27: 219–226. Measuring unbound (pharmacologically active) se- it marked inter-individual variation, resulting in large diferences rum concentrations may be of value in certain settings, particularly in serum drug concentrations at steady-state among patients re- for phenytoin. The use of serum have been identifed, no clear polymodal distribution in genotypes drug concentrations in the treatment of epilepsy is discussed com- has been identifed [7,8]. Basic pharmacokinetic principles The main pharmacokinetic properties are determined by the Why do individuals respond differently to processes of absorption, distribution, metabolism and excretion the same drug concentration? Many of these are not un- rate and extent of absorption can vary with the type of formula- derstood completely. Because the epilepsies are heterogeneous in terms of and reducing the fuctuation in serum drug concentrations during aetiology, underlying mechanisms, type and extent and location of a dosing interval [3]. Improved tolerability, related to avoidance of structural abnormalities (if present) and clinical manifestations, it excessively high peak serum concentrations during the absorptive is no surprise that the type and severity of epilepsy greatly afect the phase, has been demonstrated with sustained-release tablets of car- response to any given drug concentration. Among 40 well-controlled patients with generalized because the efects of these drugs on the brain tend to add up. The drugs acting by diferent mechanisms, irrespective of the serum median number of seizures during the frst year of epilepsy was fve concentration of individuals drugs. The within the same individual, not only in relation to utilization of dif- fact that for some drugs the reference serum concentration ranges ferent concomitant medications. This is an important point, ofen tolerance (see Chapter 7), is seen most frequently with benzodiaz- overlooked by non-specialists. Because of the development of tolerance ed that the lower limits of the commonly quoted reference ranges to the sedative efects of these drugs, patients treated chronically should be disregarded, and that any concentration up to the upper with benzodiazepines or barbiturates may tolerate well serum drug limits of these ranges should be considered as potentially therapeu- concentrations that would be very toxic and even cause coma in tic [10]. With phenobarbital, tolerance to A factor that afects the response to a given serum concentration sedative efects usually does not entail a simultaneous loss of anti- of a drug is the presence or absence of comedications. Time to peak Time to Plasma Reference Reference concentration steady- Half-life* protein range range Drug (h) state (days) (h) binding (%) (µg/mL) (µmol/L) Active metabolites Carbamazepine 4–8a 2–4 5–50 c 75 4–12 17–51 Carbamazepine-10,11-epoxide Clobazam 1–3 2–7 10–48 85 0. Pharmacokinetic Optimization of Therapy 127 whose therapeutic value during chronic treatment is ofen limited activity, as demonstrated by the relatively rapid onset of efect in by full or partial loss of efcacy. The latter observation may be explained by more rapid comedications and adaptive changes at the site of drug action, other brain penetration afer intravenous dosing, or by a diferent mecha- factors contribute to variability in the relationship between serum nism underlying drug response in diferent clinical situations. In fact, these plex time course, with the intensity of efects failing to mirror the ranges are simply representative of the serum concentrations at changes in serum concentration over time. If known, the ‘therapeutic range’ is clinically more useful possible confounding efects related to production and elimination than the ‘reference range’; for example, if a patient is known to have of active metabolites. Interestingly, in the case of valproic acid, a become seizure free at concentrations below the lower limits of the delay in the onset of suppression of the photoconvulsive response ‘reference range’, those concentrations can be regarded as ‘therapeu- does not necessarily imply a delay in blocking other types of seizure tic’ for that patient, and there will be no need to increase dosage. For example, a drug concentration 40 below the reference range in an individual with uncontrolled sei- 15 30 zures and no side-efects will give the clinician greater confdence in increasing dosage, and may help in deciding the magnitude of the 10 f 20 dosage increment. Based on knowledge of concentration–response 5 10 relationships in specifc seizure types, physicians can also elect to aim initially at a predefned target drug concentration, rather 0 11 12 13 14 15 16 17 18 19 20 21 than at a target maintenance dosage. Decisions must also take into Time(hours) consideration the patient’s attitudes; for example, if an individual Valproate-Na is likely to be very distressed by occurrence of another seizure, it 600 mg P. Conversely, lower concen- suppression of the photoconvulsive response (expressed as sensitivity trations may be targeted whenever tolerability concerns outweigh range, i. Note that complete suppression of the photoconvulsive response is delayed with section ‘When should drug concentrations be measured? To ensure optimum accuracy in es- tablishing therapeutic concentrations, sampling time must be standardized carefully, and at least two determinations should be obtained on diferent dates, in order to assess the variability of the concept of individual therapeutic the estimate. It is also important to remember that even carefully concentrations and interpretation of determined therapeutic concentrations need to be interpreted fex- serum concentrations in the clinical ibly, because the patient’s sensitivity to a given drug concentration setting may change over time. In other words, once dosage has concentrations been adjusted on the basis of clinical response and an optimal ef- The practice of monitoring serum drug concentrations, intro- fect has been achieved, the concentration associated with such an duced in the 1960s, has had a major role in improving the quality outcome can be measured and considered as an estimate of the of epilepsy care. Depending on the have been discovered, and serum drug concentration measure- characteristics of the individual, an optimal response may be either ments have contributed greatly to stimulating awareness about the sustained seizure freedom, or the best compromise between reduc- need to tailor dosage to the individual patient [1]. For ex- however, that few patients in that trial were treated with pheny- ample, if a few years later the same individual experiences a seizure toin, the drug for which measurement of serum concentrations is breakthrough, a second measurement of the serum drug concentra- particularly useful. To start with, if at the time of the seizure breakthrough the drug concentration is if the concept of individualized therapeutic drug concentrations found to be lower than the previously established therapeutic con- is accepted, a case can be made for determining serum drug con- centration, there is a strong indication that the relapse was caused, centrations in every individual afer reaching steady state on the depending on clinical context, by either a change in compliance initial target maintenance, and afer any appropriate dose increases or a change in drug disposition under the infuence of physiolog- if dosage increments were necessary (Table 10. Knowledge of derived from these measurements can allow determination of the the serum concentration at which that individual had responded concentration–response relationship within a specifc individual. For example, oral contraceptives are Poor adherence is a common reason for inadequate clinical re- known to cause a marked but variable decrease in serum lamotrig- sponse in people with epilepsy. If the individual therapeutic concentration low in 40% of patients with epilepsy [19] and 33% in children with of lamotrigine is known in a woman with well-controlled epilep- epilepsy [20]. Compliance prob- found in a recent study on the consequences of a fall in serum lam- lems are suggested by unusually low and variable concentrations, otrigine concentrations during pregnancy [17]. In this situation, dosage assessment of the drug concentration will be useful in identifying • When a change in pharmacokinetics is expected (e.

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Hum neurodestructive cytokine produced by glia in the hum an glau­ G enet 2000;107:404-5 viagra with dapoxetine 100/60 mg fast delivery. Matrix m ctalloproteinasc and tum or gene in the etiology of prim ary open angle and exfoliative glau­ necrosis factor a in glaucomatous optic nerve head purchase genuine viagra with dapoxetine on-line. Cloning viagra with dapoxetine 100/60 mg with mastercard, modeling, and chrom o­ signals induction of nitric oxide synthase-2 in hum an optic nerve somal localization for a small leucine-rich repeat proteoglycan (Sl. Induction of heat shock protein m ouse retinal ganglion cell layer is induced in vivo by the excitatory 72 protects retinal ganglion cells in a rat glaucoma model. Immunolocalization of heat mcthylcntetrahydrofolate reductase gene is a genetic risk factor for shock proteins in the retina of normal monkey eyes and monkey eyes prim ary opcn-anglc glaucoma. Association of an interleukin 1 alpha pseudoexfoliation syndrom e and pscudoexfoliation glaucoma. This is followed by an invagination into the although the association with other ocular and systemic optic cup referred to as the lens pit at 29 days of gestation. The epithelium proliferates to differentiate and recessive inheritance patterns have been documented. Л classification of the most frequent subtypes of congenital New fibers arc added to the fiber mass throughout life (creat­ cataracts is provided in Table 19. Any deregulation in these mechanisms leads to formed retina and non-development of lens,” while an loss of transparency of the lens, resulting in variable degrees absence of lens results in loss of vitreous volume leading to of opacification. The past two decades Using animal models, various developmental genes have provided an extensive amount of information on the were found to be expressed in the lens at different stages of genetics of inherited cataracts, which present a significant growth and development. Congenital cataracts due to other causes, such as infection (rubella, syphilis, toxo­ When the newly formed lens fibers elongate posteriorly, the plasmosis), trauma, and drugs, will not be discussed. The a crystal­ lins are synthesized in the epithelial cells, while the struc­ Associated to See Table 19. The gcnetic background of Weiii-Marchesam syndrome inherited cataracts is highly heterogeneous and their Craniofacial HallermanivStreifr syndrome underlying genetic characteristics remain incompletely malformations Rubinstein-Taybi syndrome characterized to date. Various genes play a role in lens development, and a ВЮск-SuizberRer syndrome mutation in one or more of these genes can result in lens Ichthyosis opacity associated or not with various other ocular malformations such as anterior segment dysgenesis, iris Chromosomal Numeric Trisomy 8. Autosomal dominant Autosomal dominant und interaction between ectoderm and keratitis. Mutations that severely disrupt protein function a critical role in the maintenance of lens transparency. W hen mutations More of these genes and protein functions are yet to be affect protein function only mildly, a less severe form of the fully characterized. Mutations in modification in their structure, causing loss of transpar­ the same gene as well as the same mutation in one gene ency and leading to scattering of light. These the person and the environment constituted 38% and 14% recurring observations limit the usefulness of molccular respectively. The study important, with heritability contributing 53% to 58% of of additional large pedigrees with affected and unaffected cataract risk and environmental factors explaining 26% to individuals will provide an opportunity to further charac­ 37% of variance. Unlike nuclear cataracts, the age of a terize phenotype variability and possibly identify novel person explained only 1 1 % to 16% of the variance of corti­ cataract genes and mutations. Although there has been an improvement in the understanding of the nature of adult- Several epidemiologic studies have shown clear evidence onset cataract using genetic and molecular biology tech­ that genetic factors contribute to the pathogenesis of nologies, more work is warranted to dissect the complex Е ngure 19. Retroillumination view of a typical epinuciear opacity related to hyperferritinemia in

The tendons of these muscles converge and unite to form a single order 100/60 mg viagra with dapoxetine visa, exceedingly strong tendon cheap viagra with dapoxetine 100/60mg. The patella functions as a sesamoid bone within the quadriceps tendon discount 100/60mg viagra with dapoxetine otc, with fibers of the tendon expanding around the patella and forming the medial and lateral patella retinacula, which help strengthen the knee joint. These fibers are called expansions and are subject to strain; the tendon proper is subject to the development of tendinitis. The deep infrapatellar and prepatellar bursae also may concurrently become inflamed with dysfunction of the quadriceps tendon. The deep infrapatellar bursa is held in place by patellar tendon which is an extension of the common tendon of the quadriceps tendon. The quadriceps tendon is made up of fibers from the four muscles that comprise the quadriceps muscle: the vastus lateralis, the vastus intermedius, the vastus medialis, and the rectus femoris. The bursa serves to cushion and facilitate sliding of the patellar tendon over the tibia. The bursa is subject to inflammation from a variety of causes with acute trauma to the knee and repetitive microtrauma being the most common. Acute injuries to the bursa can occur from direct blunt trauma to the anterior knee from falls onto the knee as well as from overuse injuries including running on uneven or soft surfaces or 937 jobs that require kneeling or crawling on the knees like carpet laying and scrubbing floors. If the inflammation of the bursa is not treated and the condition becomes chronic, calcification of the bursa with further functional disability may occur (Fig. Gout and other crystal arthropathies may also precipitate acute deep infrapatellar bursitis as may bacterial, tubercular, or fungal infections. Lateral radiograph of the right knee showing an osseous mass attached to the tibial tubercle. The mass extends to the inferior aspect of the patella and is surrounded by several ossified fragments. Infrapatellar bursal osteochondromatosis associated with unresolved Osgood-Schlatter disease. Physical examination of the patient suffering from deep infrapatellar bursitis will reveal point tenderness over the anterior knee. If there is significant inflammation, rubor and calor may be present and the entire area may feel boggy or edematous to palpation. At times, massive effusion may be present which can be quite distressing to the patient (Fig. Active resisted extension and passive flexion of the affected knee will often reproduce the patient’s pain. If calcification or gouty tophi of the bursa and surrounding tendons are present, the examiner may appreciate crepitus with active extension of the knee and the patient may complain of a catching sensation when moving the affected knee, especially on awaking. Occasionally, the deep infrapatellar bursa may become infected, with systemic symptoms, including fever and malaise, as well as local symptoms, with rubor, color, and dolor being present. Effusion associated with deep infrapatellar bursitis can be appreciated by displacing the patella. Based on the patient’s clinical presentation, additional testing may be indicated, including complete blood cell count, sedimentation rate, and antinuclear antibody testing magnetic resonance imaging or ultrasound imaging of the affected area may also confirm the diagnosis and help delineate the presence of other knee bursitis, calcific tendinitis, tendinopathy, triceps tendinitis, or other 938 knee pathology (Fig. Rarely, the inflamed bursa may become infected and failure to diagnosis and treat the acute infection can lead to dire consequences. Radiograph demonstrating high-energy tibial plateau fractures include primary fracture lines that involve both tibial condyles, severe impaction and comminution of one or both articular surfaces, and fracture extension into the shaft. A,B: Magnetic resonance images of the knee showing abnormal mass in the infrapatellar region consistent with deep infrapatellar bursitis. A linear high frequency ultrasound transducer is placed over the previously identified patella in a longitudinal orientation (Fig. A survey scan is taken which demonstrates the hyperechoic margin of the skin and subcutaneous tissues, the superficial infrapatellar bursa, the patellar tendon, and the deep infrapatellar bursa beneath it (Fig. After the skin and subcutaneous tissues, the patellar tendon, and the deep infrapatellar bursa are identified, the bursa is evaluated for enlargement, inflammation, crystals, rice bodies, hemorrhage, and infection (Figs. The patella and patellar tendon are then evaluated for abnormalities including infections, anatomic abnormalities, and fracture (Fig. Color Doppler may help identify neovascularization and hyperemia associated with patellar tendinopathy. Correct longitudinal position for ultrasound transducer for ultrasound evaluation of the deep infrapatellar bursa. Longitudinal ultrasound image of the knee joint demonstrating the deep infrapatellar bursa lying beneath the patellar tendon. Longitudinal ultrasound image of the knee joint demonstrating deep infrapatellar bursitis. Longitudinal ultrasound image demonstrating bursitis of the deep infrapatellar bursa. The osteophyte just distal to the bursa may be serving as the nidus for the inflammatory process. Longitudinal ultrasound image demonstrating a moderately large deep infrapatellar bursitis. The use of ultrasound guidance can simplify needle placement when injecting or aspirating the deep infrapatellar bursa. The pes anserine bursa lies between the combined tendinous insertion of the sartorius, gracilis, and semitendinosus muscles and the medial tibia (Fig. The bursa is subject to the development of inflammation after overuse, misuse, or direct trauma (Fig. The medial collateral ligament often also is involved if the medial knee has been subjected to trauma. The medial collateral ligament is a broad, flat, band-like ligament that runs from the medial condyle of the femur to the medial aspect of the shaft of the tibia, where it attaches just above the groove of the semimembranosus muscle (Fig. The medial collateral ligament is crossed at its lower part by the tendons of the sartorius, gracilis, and semitendinosus muscles. Axial (A) and sagittal (B) fat-suppressed proton density-weighted images demonstrating an inflamed pes anserine bursa (arrows) along the medial tendons. The medial collateral ligament is a broad, flat, band-like ligament that runs from the medial condyle of the femur to the medial aspect of the shaft of the tibia, where it attaches just above the groove of the semimembranosus muscle. The pes anserine bursa lies beneath the pes anserine tendon, which is the insertional tendon of the sartorius, gracilis, and semitendinosus muscles to the medial side of the tibia (Fig. The bursa serves to cushion and facilitate sliding of pes anserine tendon over the tibia. The bursa is subject to inflammation from a variety of causes with acute trauma to the knee and repetitive microtrauma being the most common. Acute injuries to the bursa can occur from direct blunt trauma to the medial knee as well as from overuse injuries including running on hills or sudden increases in the distance that one runs.