Ying Cheong

• Senior Lecturer, Subspecialist in Reproductive Medicine
• and Surgery, Southampton Fertility Unit, University of
• Southampton School of Medicine, Southampton

Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis erectile dysfunction treatments vacuum buy cialis extra dosage cheap. It has since become an umbrella term that encompasses a diverse group of inherited neurological diseases characterized by the defining feature of prominent spastic paraparesis erectile dysfunction medication injection purchase 50 mg cialis extra dosage overnight delivery. Also impotence 20s buy generic cialis extra dosage online, apart from degeneration of pyramidal tracts in the spinal cord erectile dysfunction on coke cialis extra dosage 50mg mastercard, significant heterogeneity is present erectile dysfunction circumcision purchase cheap cialis extra dosage on-line. Degeneration of both anterior and lateral (crossed and uncrossed) pyramidal tracts was observed erectile dysfunction over the counter drugs cheap cialis extra dosage american express. Schwarz and collaborators [11, 12] reported severe demyelination in axons in pyramidal tracts, with lateral pyramidal tracts more severely affected than anterior pyramidal tracts. At the third lumbar level, anterior columns were relatively spared while lateral columns were demyelinated. At the eighth cervical level, the fasciculus cuneatus (Burdach) of dorsal columns was intact, while the fasciculus gracilis (tract of Goll) showed demyelination. At the second cervical level, in the lateral pyramidal tract, loss of myelin was less than that described above, while the dorsal columns remained demyelinated. At the decussation of pyramids in the medulla, the pyramids were pale, and demyelination was observed along the medial and lateral surfaces of the gracile nuclei. This was a 64-year-old woman with onset at age 40 of progressive spastic paraparesis. Neurologic examination showed bilateral ptosis, reduced bulbar motility and anisocoria, perioral dyskinesis, spastic tetraparesis, and bilateral Babinski signs. The most prominent findings at autopsy were crystalloid deposits (cubic or trapezoid shapes) accompanied by astrocytic gliosis and microglial proliferation. Furthermore, generalized muscle atrophy, contractures, dysphasia, and alternating, rapid horizontal eye movements were observed. The brain was highly atrophic (1100 g), and atrophy of the corpus callosum was readily noticed. Lateral and anterior pyramidal tracts were atrophic, and loss of nerve fibers was seen in dorsal spinocerebellar and posterior columns, in particular in fasciculus gracilis. Parvalbumin immunostaining of neurons was reduced, and calbindin D28K immunoreactivity was markedly reduced. On pathologic examination, practically complete loss of Betz cells in the precentral gyrus was seen. Grumose degeneration [18], comprising degenerating axons, was Neurodegeneration, First Edition. Romana Hoftberger, Clinical Institute of Neurology, Medical University Vienna, Vienna, Austria. Although most fibers decussate in the caudal medulla, a minority of fibers descend uncrossed as the ventral corticospinal tract (not shown). Depigmentation of substantia nigra was severe, and spinal cord and ventral roots were atrophic. Neurons throughout the brain accumulated large amounts of lipofuscin, and they were markedly reduced in number. Pyramidal tracts were atrophic, and loss of neurons was detected readily in the spinal cord anterior horn. Additionally, the dorsal spinocerebellar tract and fasciculus gracilis were atrophic. The clinical picture consists of spastic paraplegia and impaired vibratory sensation. Additional signs include microcephaly, lumbar lordosis, and hyperreflexia in the lower extremities; corpus callosum agenesis and enlargement of lateral and third ventricles can be seen on brain imaging. Additional symptomatology can include optic atrophy, cerebellar ataxia, impairment of vibratory sensation, scoliosis, axonal neuropathy, and pes cavus. The clinical picture consists of severe lower limb spasticity, upper extremity spasticity, and ataxia (not observed in all patients). Bilateral lamellar cataracts, delayed age of bone, shallow acetabulum, small carpal bones, dysplastic cranial base, and decreased muscle mass are other features. Age of onset was the first year of life in a proband but 22 years in his mother and 37 years in an earlier generation. Ocular abnormalities, myopia, and chorioretinal dystrophy were reported along with persistent vomiting and gastroesophageal reflux. Age at onset of symptoms can vary widely, and although many cases are pure, a number of complex cases are known. Neuropathologic evaluation in a small number of cases has revealed atrophy of the spinal cord due to degeneration of the pyramidal tract, accompanied by spongiosis with ubiquitinimmunopositive granules. The clinical picture consists of pure spastic paraplegia plus distal impairment of vibratory sensation. The age of onset was 16 years and the clinical picture consisted of lower limb atrophy, weakness of small muscles of the hands, impairment of vibration sensation and joint position sense, pes cavus, and impairment of gait, but without spasticity. Peripheral axonal neuropathy is frequent, and cerebellar ataxia has been reported. Additional signs can include parkinsonism, retinopathy, pseudobulbar signs, urinary dysfunction, peripheral motor or sensorimotor polyneuropathy, and distal amyotrophy. Kjellin [52] in 1959 reported two pairs of siblings with spastic paraplegia, wasting of distal muscles, mental retardation, and central degeneration of the retina [53]. Age of onset varies between 5 and 24 years and the clinical picture is mostly pure. Features are quadriplegia, aphasia, and impairment of vision and sphincter function. The clinical picture consisted of spastic paraplegia with distal motor neuropathy, mild cognitive dysfunction, and pes cavus. Other presentations can be consistent with distal spinal muscular atrophy, pure spastic paraplegia, and peroneal muscular atrophy; the latter has been accompanied by pyramidal signs and symptoms [56]. In addition to spastic paraplegia, patients suffer from mental retardation, this form of spastic paraplegia was reported by Al-Yahyaee et al. Electron microscopic examination of leukocytes revealed electron-dense membranebound vacuoles. The clinical picture consists of spastic paraplegia, pes cavus, and slowing of motor and sensory conduction in the lower extremities. Age at disease onset has ranged from 2 to 19, with difficulties in walking and dysarthria. Drooling, pseudobulbar affect, short stature, distal amyotrophy, and cerebellar signs were also observed. Additional signs and symptoms have included skeletal abnormalities, cerebellar signs, and polyneuropathy. Onset was in adulthood, with speech decline, personality changes, psychosis, and cerebellar dysfunction in addition to spastic paraplegia. In addition to spastic paraplegia, axonal neuropathy and cerebellar oculomotor dysfunction have been observed. It was reported in 1944 [67] in a family with hypotonia at birth, inability to raise the head, reduced motor milestones, generalized muscle atrophy, and hyperreflexia. Ataxia, dysarthria, athetoid movements, and spastic paraplegia were also observed. Onset is in infancy, and associated signs included sensorineural hearing deficits and persistent vomiting due to hiatal hernia. Onset of disease varied between 12 and 21 years with distal sensory loss, mild cerebellar signs, and saccadic ocular pursuits. Although originally described in a consanguineous Arab Israeli family in 1985, the locus was refined by Blumen et al. Onset is in infancy, with abnormal skin and hair pigmentation, skeletal deformities, and sensorimotor neuropathy. The disease starts in childhood, and associated features can include spastic dysarthria and pseudobulbar signs. This identification remains questionable, and Rugarli and colleagues have reported that this mutation is a benign polymorphism [83]. The clinical picture consisted of spastic paraplegia, hyperreflexia, pes cavus, and atrophy of the lower limb muscles. Additional signs and symptoms are clonus, dystonia, seizures, cognitive decline, and cerebellar signs. Other signs included Babinski sign, involvement of upper extremities, and impairment of vibration sense. The clinical picture consists of spastic paraplegia and peripheral sensorimotor neuropathy. This form of spastic paraplegia was reported in an Italian family by Orthmann-Murphy et al. The clinical picture consisted of spastic paraparesis, pes cavus, dysarthria, loss of subtle movements of fingers, and cerebellar signs. Spastic bladder, upper limb cerebellar dysmetria, congenital cataracts, and pes cavus were also observed. All patients developed cataracts, cerebellar ataxia, dementia, hearing loss, and axonal neuropathy. The clinical picture consists of spastic paraplegia, hyperreflexia, and mild weakness in the upper extremities. Symptoms noticed at birth included microcephaly and hypotonia which eventually evolved to hypertonia. Other signs include high palate, wide nasal bridge, short stature, hypermobility of joints, and genu recurvatum (a knee joint deformity, such that the knee bends backwards). Recently identified cases have parkinsonism and retinal abnormalities as additional features [103]. Clinically, there is spastic paraplegia, mental retardation, foot contractures, dysarthria, dysphagia, strabismus, and optic hypoplasia. The clinical picture consists of dysmorphic features, developmental delay, brachycephaly, microcephaly, dental crowding, dysarthria, and dysmetria. The disease started at age 7 with impairment of vision, with walking difficulties several years later. Nerve biopsy revealed decreased numbers of large-diameter nerve fibers as well as onion bulbs. The five affected siblings demonstrated signs and symptoms of infantile hypotonia, severe mental retardation, quadriplegia, and strabismus. They also demonstrated signs of pseudobulbar palsy, compulsive laughter, and sphincter impairment. The clinical picture consists of spastic paraplegia or quadriparesis, dystonic postures, dementia, and axonal neuropathy. In addition to spastic paraplegia, axonal demyelinating motor neuropathy and optic atrophy are present. The clinical picture consisted of quadriplegia, microcephaly, psychomotor retardation, seizures, and dysmorphic features. The disease started in infancy, and the clinical picture comprises mental retardation, contractures, pes equinovarus (club foot), microcephaly, dysmorphic features, inappropriate laughter, and short stature. The clinical picture consists of quadriplegia, developmental delay, marked kyphosis, and pectus carinatum. Upper limb spasticity was also noticed as well as pes cavus, urinary problems, slight postural tremor, and impaired vibratory sensation. Patients also have loss of vibratory sensation at the ankles, and a couple of those affected have a mild foot deformity. Age of onset was in infancy, and the clinical picture in addition to spastic paraplegia consisted of pes equinovarus, amyotrophy, and a severe sensorimotor polyneuropathy. Age of onset is early childhood, and associated symptoms include optic atrophy, nystagmus, and mild neuropathy. This is not surprising, given the great length and extreme polarity of corticospinal axons, which can extend to 1 meter in length. Splice variants exist for both which lack a 32 amino acid stretch encoded by exon 4 [118]. The N-terminal half mediates interaction with proteins that recruit spastin to various cellular compartments. Disease onset was before the age of 1, and the clinical picture includes Achilles tendon contractures and amyotrophy. Age of onset varied from infancy to 8 years, and the clinical picture is notable for slowly progressive lower extremity spasticity. A number of gene products are not shown, pending more detailed studies of their sites of action. The N-terminal half of spastin contains two distinct domains that can explain this isoform specificity. M87 spastin is required for completion of abscission at the terminal stage of cytokinesis, when the midbody is densely packed with an anti-parallel array of microtubules. In cells lacking spastin, the microtubule disruption that normally accompanies abscission does not occur, suggesting that it requires spastin-mediated microtubule severing [120]. Thus, this exemplifies how microtubule regulation can be linked to membrane modeling events through spastin. Cells lacking spastin have increased tubulation of endosomal tubular recycling compartments, with resulting defects in receptor sorting. In a zebrafish model, spastin was required for axon outgrowth during embryonic development [142], reminiscent of effects of atlastin-1 depletion in rat cortical neurons [136].

The rub is that when you see transverse process fractures erectile dysfunction pump uk cheap cialis extra dosage 50 mg free shipping, you should look for other erectile dysfunction nicotine purchase cialis extra dosage 40 mg with mastercard, potentially unstable fractures elsewhere in the spine erectile dysfunction names order cialis extra dosage from india. Insufficiency Fractures of the Sacrum these pathologic injuries result from the inability of abnormal bone to withstand normal stress and are seen after radiation therapy or secondary to postmenopausal or steroid-induced osteoporosis impotence psychological cialis extra dosage 200mg free shipping. In addition to the sacrum erectile dysfunction meds list cheap cialis extra dosage 50mg overnight delivery, they can occur in the lower extremities erectile dysfunction lyrics cheap 60 mg cialis extra dosage fast delivery, ilium, and pubis. The major finding is linear defect running vertically (parallel to the sacroiliac joints) in the sacral alae, usually at the first through third sacral segments. Spinal Cord Injury without Radiologic Abnormality this condition presents as myelopathy after a traumatic event but the imaging of the cord is normal. The cause is usually a hyperextension injury and patients may present with central cord symptoms. One can have a huge cache of facts, but applying that genius to reading the studies is a whole different ball of ear wax. We hope to present to the reader in this chapter the ultimate Super-Google/Bing/PubMed "Search Engine" for identification and understanding the findings. However, the ultimate compliment for the radiologist is that "She is brilliant and she has great eyes. Reading neuroradiology requires an organized, thorough review of all images of a study. Perhaps create a "macro template" on your cervical spine speech recognition program that forces you to make a comment about the patency of the vertebral arteries or status of the thyroid gland or visualized portions of the brain. Use the clinical information at hand to help guide your interpretation of the images. This means searching the medical record for clinical indication for the scan, physical examination findings, and overall clinical assessment of this patient. Not only will this help guide your review of the case, it will provide the basis for a more succinct and clinically relevant interpretation of a scan. No clinician wants to read a report that gives a differential diagnosis including congenital, vascular, infectious, inflammatory, demyelinating, traumatic, degenerative, toxic, metabolic, and neoplastic processes. Try to get a sense of what the clinical picture is, so that you can provide a more relevant and clinically useful differential diagnosis. While it might seem tedious at first, recognizing that a lesion has been present on a previous examination or is a new finding is really helpful in your overall assessment. Also, it helps to review the previous report to make sure all findings previously described are accounted for on your scan. Reading a Brain Computed Tomography Scan the approach to reading a case varies according to the clinical indication for the study and personal habits. As long as the modus operandi is consistent, thorough, and organized, the exam will be read appropriately. Start by taking the central to peripheral approach, looking at each image from first slice to last individually. Is there blood in the interhemispheric fissure, ventricles (beware the occipital horns-they are blowing for you), or sylvian fissure Are the ventricles shifted from their normal position, and are the cisterns or sulci effaced by mass effect Assess to what extent structures are shifted, because it may require an emergent intervention to save the patient. Are all the basal cisterns effaced and the ventricles small, suggestive of diffuse cerebral swelling Be careful-subtle sulcal effacement (with even more subtle density changes) may be the only clue to early stroke. Asymmetry of the lateral ventricle size is not uncommon, 605 606 Chapter 17 Approach and Pitfalls in Neuroimaging but it should heighten the search for a unilateral obstructive mass or septation/cyst at the foramen of Monroe. If there is hydrocephalus, is it communicating (all ventricles enlarged) or noncommunicating (isolated ventricular enlargement) By the analysis of the ventricles and cisterns, you should have determined whether a surgical emergency is present. Is there brain swelling requiring steroids and diuretics or surgical decompression (careful to look in the posterior fossa for cerebellar infarcts that swell, obstruct the fourth ventricle, and lead to acute supratentorial hydrocephalus) Is there bilateral insula or cingulum or temporal lobe edema, suggestive of herpes encephalitis requiring emergent antiviral treatment Is there added density to the subarachnoid space and mild hydrocephalus, suggestive of meningitis Next on the agenda is looking at the periphery of the brain for extraaxial collections. You may already have a suspicion that the patient might have mass effect on the basis of effacement of sulci, midline shift, buckling of the gray-white matter interface, or compression of ventricles. We routinely do coronal reconstructions in soft-tissue windows for our trauma cases to have a second chance (because we have "blown it" so many times just on the axial scans) at detecting that subtle subdural. The potential pitfalls: Bilateral extracerebral collections that do not cause ventricular shift; the isodense subdural hematoma detected by noticing that the white matter is not approaching the periphery of the brain and there is absence of normal sulcation. On the peripheral pass through the brain you may detect soft-tissue scalp swelling, which hints to the site of the head trauma. Pay particular attention to the underlying brain as well as to the contrecoup side. If you detect a skull fracture (after your later review of the bone windows), be wary about epidural hematomas over the temporal lobes (middle meningeal artery) or near venous sinuses. An initial run-through from central to peripheral will identify any obvious areas of density differences, suggestive of hemorrhage or necrosis. Hypertensive bleeds occur most commonly in deep gray matter structures near the ventricles, so start there. Common trauma sites are the inferior frontal lobes along the gyrus rectus and the anterior temporal lobes from impact along the greater wing of the sphenoid. Work outward to detect cortical hemorrhages from infarcts or contusions or amyloid angiopathy. Again, you may be directed to look at a particular location coup or contrecoup on the basis of ventricular displacement, scalp findings, or peripheral collections. For the stroke evaluation, one must look for the most subtle areas of distorted architecture or density differences. If you want to call the stroke, remember the early signs of infarct: clot in the vessel, loss of insular ribbon hyperdensity, loss of distinction between basal ganglia and internal capsule, and blurring of graywhite differentiation in the periphery. Remember your major vessel vascular anatomy to help with the check for strokes and to suggest another diagnosis if the distribution does not fit. Having looked from central to peripheral and then around the periphery of the scan, it is time for the extracerebral abnormalities. Neck abscess, pharyngitis, dental abscess, mastoiditis, or otitis media in a search for a source of fever Always check the scout topogram; you will be surprised how often you will pick up cervical spine injuries, spondylosis, bone metastases, basilar invagination, platybasia, myeloma, an enlarged sella, and other conditions on the basis of the scout view. Use narrow window settings to view images for subtle stroke density differences and intermediate ones for subdural hematomas. With everything electronic and multiplanar, you can customize your settings to maximize detection of abnormalities based on clinical indications. Chapter 17 Approach and Pitfalls in Neuroimaging 607 Use the same routine: Start from central to peripheral. If that scan is hard to recognize, then it is likely that a mass displaces the midline, and that mass will be better seen on axial scans. On the midline image, take a look at the corpus callosum, the sella, the clivus, the superior sagittal sinus, vein of Galen, straight sinus, pineal gland, fourth ventricle, cerebellar tonsil position (5 mm or less below the foramen magnum is normal), cervical spinal cord, upper cervical spine, and nasopharynx. Are any of these structures displaced upward or downward, not present at all, or of abnormal signal intensity From the midline, go to the more peripheral images and make sure you search for extraaxial collections, the vascular flow voids, and abnormal signal intensity (usually high) to suggest hemorrhage. Again, check the temporal tips and the temporal lobes for hemorrhage or sulcal distortion, particularly in the setting of trauma. Remember that the sagittal image is usually the only one that also gives you a good peek at the cervical spine and neck, because most brain study axial scans are prescribed from the foramen magnum and go up. Is a parotid, submandibular gland, lingual, pharyngeal, or laryngeal mass present In centers with active stroke intervention programs, you may be required to perform a perfusion scan to demonstrate the ischemic penumbra. In some settings, this will lead to medical therapy designed to optimize cerebral blood flow (hypertensive, hypervolemic therapy) or thrombolysis. Subtle differences exist between them but often these are best to identify increased water. As you analyze the ventricles and cisterns for displacements, the subdural and epidural spaces for collections, the deep gray matter structures for signal intensity abnormalities, and the peripheral cortex for subtleties of intensity differences and mass effect, recall how easy things seemed during your medical school training. Is there abnormal enhancement of the meninges, dura, cisterns, exiting nerves, ependyma, or extraaxial fluid collections Hopefully reviewing phase maps and looking at the choroid plexus calcification signal intensity will aid you here. Is the expected curvature of the spine maintained or is there straightening, exaggerated curvature, or subluxation present at any particular level Next assess vertebral body heights and disk spaces, as well as the facet relationships on either side. Are there endplate degenerative changes present or do they seem more aggressive and destructive Coronal imaging is very useful in assessing the relationship between the occipital condyles, lateral masses of C1, and the C2 vertebral bodies. Any abnormalities in this sequence of evaluation should raise suspicion for pathology at that particular level and alert you to examine that level in more detail on your axial images. If you suspect an abnormality in cord signal, take a look and confirm the abnormality on the axial images, because spine imaging is notorious for artifacts creating pseudolesions. Proceeding level by level, an assessment of canal and foraminal patency should follow. Is there a disk herniation, facet hypertrophy, or intraspinal/foraminal mass or fluid collection to explain the narrowing you are observing Remember that cord compressive pathology deserves a call to the clinical team, because urgent decompression might be necessary. If you see an asymmetry, make an assessment of the scope of the abnormality, defining the anterior, posterior, superior, inferior, medial, and lateral extent of the abnormality. Then perform the same process for the soft tissues in the neck, using symmetry as your friend. In such cases, it is a good idea to have a complete idea of the reason for the scan, the type of treatment the patient has received (surgery, chemotherapy, radiation), and to be aware of any soft-tissue or bony reconstructions performed. Once you are ready to review the images, it is important to look at your scan side by side with the previous scan, to assess for potential interval changes. Keep in mind that all changes do not necessarily mean tumor is back; there are a host of expected posttreatment changes that can be appreciated on follow-up examinations. Finally, an understanding of patterns of tumor spread for particular tumor types is very helpful. If so, take a careful look at the skull base foramina and respective soft tissues for evidence of invasion or denervation injury. Next, take a look at the cervical lymph nodes and identify any that appear pathologic based on size, number, morphology, necrosis, perinodal inflammation, or calcification. Then evaluate the salivary glands for any asymmetry in terms of size or enhancement. Make sure the major vessels in the neck opacity if the study is performed with contrast. Do not forget to take a peek at the brain, orbits, paranasal sinuses, cervical spine, and lung apices for abnormalities before you conclude your review. At no extra cost we have included tables of useful radiologic gamuts in the online Appendix at ExpertConsult. It is only through reviewing numerous cases day after day that one obtains a mental image of the normal anatomy from which deviations can be readily identified. Thus, they can scan an image at light speed and still detect the subtlest abnormalities. The trainees who view the most cases will be served well in this regard-they will have the easiest time detecting lesions. It is true that the anatomy is complex, but the best way to overcome this fear is to have a systematic approach from one scan to the next. We believe that you can evaluate a lesion with very little knowledge-how do you think we got this far You really do not have to know that much about the company (pathology) if you just follow the basics. Table 17-1 provides useful information concerning the characterization of lesion types with intensity information. If a lesion decreases in intensity as the T2 weighting increases, you are more likely to be dealing with a lesion that has susceptibility effects. Several criteria are critical here: mass effect, atrophy, texture, edema pattern, extent of lesion, nature (solid versus cystic), number (single or multiple), distribution. Lesions possessing mass effect are usually "active," whereas those that do not may be either old or still very new (within the first hours). Examples of the former include a tumor or new stroke, whereas the latter would include an old stroke or old traumatic injury to the brain. Mass effect can be subtle, with slight effacement of sulci; however, such changes are highly significant with regard to arriving at the correct diagnosis. Although the brain parenchyma decreases with age normally, focal loss of parenchyma is significant for old strokes, traumatic episodes, postoperative changes, or treated encephalitides. For instance, oligodendrogliomas have a rather heterogeneous texture, whereas lymphomas are more homogeneous.

Note that the parapharyngeal fat (asterisks) is displaced posteromedially by this masticator space infection impotence at 46 purchase cialis extra dosage 100mg with mastercard. This may be caused by lesions in the peripheral branches of the third division of cranial nerve V erectile dysfunction market buy cialis extra dosage 100mg amex. There is marked atrophy of the left muscles of mastication (asterisk) due to V3 disease erectile dysfunction patient.co.uk doctor discount 200mg cialis extra dosage with visa. B erectile dysfunction drugs compared order cialis extra dosage 50mg with amex, the muscles (arrows) on the right in a different patient are larger than the left causes of erectile dysfunction and premature ejaculation 200mg cialis extra dosage with visa. Fibrous Dysplasia Fibrous dysplasia causes enlargement of the mandible and maxilla with expansion of the outer cortex of the bone vegetable causes erectile dysfunction buy cialis extra dosage with paypal, generally without erosion through the bone. Both of these disorders tend to expand during adolescence, are possibly related to hormonal influences, and either regress or stabilize in young adulthood. The skull and facial bones are involved in 10% to 25% of cases of monostotic fibrous dysplasia and in 50% of polyostotic fibrous dysplasia. The posterior band is attached to the posterior joint by the retrodiskal tissue, or bilaminar zone. The joint capsule itself has an anterosuperior compartment and an inferior compartment, which usually do not communicate, allowing effusions in multiple compartments. The lateral pterygoid muscle opens the jaw and inserts on the anterior portion of the disk. The medial pterygoid, temporalis, and masseter muscles close the jaw (except in lawyers). The dislocation may reduce on opening (often with a clicking sound-the "opening click") and may redislocate on closing (a closing click). A medial or lateral component in addition to the anterior dislocation (rotational dislocation) is not uncommon, said to occur in 25% to 30% of cases. Isolated medial and lateral (termed "sideways") dislocations are relatively rare; however, with a transverse component the possibility of nonsurgical reduction of the dislocation is decreased (from 46% to 9%). It may or may not be anteriorly displaced, but it is usually fibrosed in and immobile. Note how the mandibular condyle translates forward anteriorly on mouth opening to allow for disk recapture. The posterior band (white arrow), superior retrodiskal later (white arrowhead), as well as superior (black arrowhead) and inferior capsular (black arrow) attachments, are shown. E, Schematic representation of anterior disk dislocation on closed mouth view with appropriate recapture despite the dislocation on mouth opening. G, A coronal T1-weighted image shows that the disk (between arrowheads) is also medially dislocated relative to the condylar head (C). H, On mouth opening, despite its degenerative appearance, this disk (between arrowheads) does recapture appropriately between the condyle (C) and eminence (E). The degree of disk displacement is greater in symptomatic than asymptomatic individuals and recapture of the displaced disk is less frequent in patients than asymptomatic volunteers (where it is the norm). Note how the condyle shows very limited anterior translation, giving the "locked" appearance. K, Sagittal oblique T2 image shows the same anteriorly displaced disk (arrowhead), condyle (C), and eminence (E) on closed-mouth view. L, On mouth opening, the pesky osteophyte (arrowhead) limits anterior translation of the condyle (C), and the displaced disk (arrow) does not recapture. Perforations usually occur at the junction of the bilaminar zone with the posterior band. If the patient fails to respond to this noninvasive therapy and has meniscal abnormalities, plication of the disk into a more normal location or meniscal removal with or without prosthesis may be attempted. Complications related to the surgery including foreign body reactions, granular cell reactions, or avascular necrosis of the condylar head (which may also occur even without surgery). The latter may be identified as low signal intensity on all pulse sequences in the condylar head. In the long term, degenerative changes in the joint may develop and include narrowing, osteophytic bird-beaking of the condyle, eburnation, ankylosis, joint mice/loose bodies, and fragmentation. Benign Neoplasms Hemangiomas and Vascular Malformations In 1982, a new classification of hemangiomas and vascular malformations was proposed by Mulliken and Glowacki and has since been adopted. In this new design, infantile hemangiomas have been relegated to those benign neoplasms of endothelial cells that may or may not be present at birth. Congenital hemangiomas are visible at birth, whereas infantile hemangiomas are seen after a few weeks of life. This temporomandibular joint lesion shows a calcified matrix and destruction of the temporal bone making up the glenoid fossa. The differential diagnosis would include synovial chondromatosis, a chondrosarcoma, a chondroblastoma, calcium pyrophosphate dihydrate deposition disease, tumoral calcinosis, and Brown tumor, in decreasing order of likelihood. Both may have a rapid proliferative phase shortly after birth, and 50% completely resolve by 5 years of age and 72% by 7 years of age. They may be in the skin, subcutaneous tissues, or deep spaces of the head and neck. If the lesions fail to involute on their own, they may be prodded to do so with steroids, alpha interferon, or chemotherapy. The infantile hemangioma is the most common pediatric, benign neoplasm of the masticator space. This generally begins in the superficial tissues but may extend deeply into the muscles and adjacent fat of the masticator space. Kasabach-Merritt syndrome is characterized by infantile hemangiomas associated with consumptive coagulopathy, high-output congestive heart failure, and respiratory distress with or without splenomegaly. Vascular malformations are the other lesions that before 1982 were called "hemangiomas" and have been reclassified. They may be primarily venous, lymphatic, or combination lesions when they are low-flow ones. They are comprised of dysplastic vessels,are present at birth,grow during fast growth phase of the child, and persist. Klippel-Trenaunay-Weber syndrome has mixed capillary-venous-lymphatic malformations with hemihypertrophy. Percutaneous sclerosis may be employed as treatment for venous vascular malformations, even using ethanol under general anesthesia to control pain. Fluid-fluid levels are more common in lymphatic malformations than venous vascular malformations. Note how this mass (N) that is isointense to muscle in A enhances so dramatically in B. C, Different case, and same diagnosis: T2-weighted imaging shows infiltrating venous vascular malformations (h). A, Ewing sarcoma arising from the right mandible extends into the masticator space on this postcontrast axial T1-weighted image. This was an osteosarcoma that developed in a patient who underwent radiation therapy for oral squamous cell carcinoma (double bummer). They frequent the posterior triangle and axilla most commonly but can occur anywhere, detected before age 2 in 90% of cases. High flow vascular malformations contain an arterial component and may contain a nidus or a fistula. They are the least frequent of the childhood vascular malformations but may be seen with Osler-Weber-Rendu syndrome. These are basically arteriovenous malformations of the head and neck and are uncommon. Ameloblastoma A relatively common benign bony tumor of the mandible is the ameloblastoma. It is labeled benign because it does not metastasize, but it is highly aggressive locally and may have malignant growth patterns. There may be an extraosseous component to this lesion as it expands beyond bony confines. Neurogenic Tumors Other benign neoplasms of the masticator space include schwannomas and neurofibromas derived from the branches of cranial nerve V that permeate the masticator space. Isolated schwannomas are the most common neurogenic tumor of the masticator space. A small percentage of patients with neurofibromatosis may have malignant neurogenic tumors, which may affect the masticator space. Usually, the inferior alveolar canal of the mandible is eroded and expanded by malignant neurofibromas of V3, and the tumor may ascend into and through the skull base (foramen ovale) toward the Meckel cave to the gasserian ganglion. Osteosarcomas of the craniofacial region account for less than 10% of all osteosarcomas. Familial retinoblastomatosis may predispose to osteosarcomas (and other head and neck sarcomas) by virtue of the chromosome 13 oncogene. This left tonsil/lateral base of tongue squamous cell carcinoma grew into the pterygoid musculature (arrows), thereby invading the masticator space. Both of these lesions may demonstrate periosteal reaction and either a dense hyperostotic destructive mass or a lytic process in the mandible. Ewing sarcomas occur in a younger first and second decade age group than osteosarcomas, which affect patients in their third and fourth decades of life. For all mandibular or maxillary lesions, it is important to assess for cortical (erosions, defects) versus marrow (replacement of fat density/intensity) involvement. Once the bone is involved, one must be cognizant of the mental and inferior alveolar foramina to assess for perineural invasion. Always look at the pterygopalatine fossa (V2) and foramen ovale (V3) fat planes to assess for malignant spread along the nerves. Squamous Cell Carcinoma Squamous cell carcinoma of the mucosa is the most common malignancy to secondarily invade the masticator space. Typically, the squamous cell cancers arise in the region of the oral cavity (especially the retromolar trigone), oropharynx, or nasopharynx, where extension to the pterygoid musculature is not uncommon. Only the temporalis muscle is relatively spared from squamous cell carcinoma spread (except from skin cancer penetration). Metastasis Metastases to the bones of the masticator space are not uncommon and typically arise from breast, kidney, or lung cancer. The most common metastasis to the mandible is an adenocarcinoma from the breast, and mandibular involvement occurs five times more commonly than maxillary involvement. Rhabdomyosarcomas are the most common of these tumors and are generally seen in children. Fibrosarcomas and osteosarcomas have also been reported in the head and neck, often in association with retinoblastoma. Malignant neurofibrosarcomas and synovial sarcomas may also affect the masticator space. Note the remodeling of the left mandible (arrow) and posterolateral wall of the maxillary sinus. Axial T1-weighted imaging shows the high signal intensity of the prestyloid parapharyngeal space fat (arrowhead), anteromedial to the deep lobe of the parotid gland (P). Separating the prestyloid and poststyloid parapharyngeal space is the styloid musculature (asterisks). Directly behind the styloid musculature, one can identify the carotid artery (c) and jugular vein (j) within the carotid space. On computed tomography, the styloid process may be the best anatomic landmark to separate the two spaces. Now you will be served the foie gras, a fatty infiltrated region, the parapharyngeal space. The poststyloid parapharyngeal space contains the carotid sheath and has been called the carotid space by many authors. When cognoscenti refer to the parapharyngeal space, however, they are generally referring to the prestyloid portion. Only fat, lymphatics, and very small branches of the internal maxillary artery, ascending pharyngeal artery, and mandibular (V3) nerve lie within the parapharyngeal space. Occasionally, you may find ectopic minor salivary gland tissue; however, the space, like our midsections, is dominated by its fat. The parapharyngeal fat is a readily mobile and therefore is readily displaced and infiltrated by adjacent disease. By observing the direction of displacement of this fat, you can identify a lesion as arising from one of the deep spaces of the head and neck (see Table 14-1). Cystic schwannomas would be in the differential diagnosis, but concurrent enhancing solid tissue in schwannomas, not branchial cysts, should steer you to the correct Mike Trout home run diagnosis. Just do not bet the farm on it like Pete Rose, or you will never make it to the Neuroradiology Hall of Fame. Inflammatory Lesions Intrinsic inflammatory disease of the parapharyngeal space is also rare. Infections may spread secondarily from (1) mucosal infections such as tonsillitis or pharyngitis, (2) masticator space lesions such as odontogenic abscesses, and (3) parotid infections. Benign Neoplasms Primary lesions arising within the prestyloid parapharyngeal space are extremely uncommon and are usually found incidentally. Because only fat, ectopic minor salivary gland tissue, and lymph nodes are present in this region, the most common intrinsic lesions of the prestyloid parapharyngeal space are enlarged lymph nodes, either inflammatory or neoplastic. If you transplanted this mass to the parotid gland, this would be a "no-brainer" pleomorphic adenoma. After salivary gland tumors (40% to 50%), neurogenic tumors (17% to 25%), glomus tumors (10% to 14%), and lipomas may primarily arise here. As noted, parotid masses in the deep lobe are the most common benign neoplasm to invade the parapharyngeal space secondarily. If the parapharyngeal fat is displaced anteromedially, suggest the diagnosis of a deep lobe parotid mass. If the parapharyngeal fat is seen between the lesion and the deep lobe of the parotid, then the lesion is either mucosal in origin or arose within the ectopic tissue of the prestyloid parapharyngeal space.

Some mutations exhibit a dominant-negative effect of the mutant Cx32 protein on the normal Cx32 or other connexins xenadrine erectile dysfunction purchase 50 mg cialis extra dosage visa, causing abnormal gap junctions erectile dysfunction causes and treatment cheap cialis extra dosage 60 mg with visa, while others lead to loss of function whereby levels of the Cx32 protein are reduced and the resulting gap junctions are non-functional [63] erectile dysfunction natural remedies cheap 60mg cialis extra dosage otc. Prx-null mice show evidence of demyelination due to unstable myelin [67 erectile dysfunction and stress order cheap cialis extra dosage online, 70] followed by remyelination with dysregulated myelin thickness [71] and remodeling of motor nerve terminals [72] impotence 20s buy discount cialis extra dosage 50 mg on line. The mouse homolog Krox-20 is necessary for the expression of late myelin genes in Schwann cells [74] erectile dysfunction pills non prescription order cialis extra dosage 40mg with visa. Schwann cells in Krox-20 knockout mice are not able to differentiate fully and thus do not form compacted myelin [74]. Dominant Egr2 mutations cause a disruption in this transcriptional regulation by decreasing the affinity of Sox10 to the binding site, leading to a disruption of the myelination program [77]. A-type lamins have also been proposed to protect cells from physical damage, and to be important in the functioning of transcription factors needed for adult stem cell differentiation [80], as well as for genomic stability [81]. A defect in their function may specifically affect peripheral nerves, which have high metabolic demands. It is also unlikely that Gars mutations lead to a defect in an unknown function in the translation process, unless the protein has an unrecognized role in translation specifically in peripheral nerves [94]. Decreased mitochondrial transport may lead to depletion of the much-needed energy supply in long peripheral nerve axons. Recessively inherited mutations cause loss of its function in mitochondrial fragmentation [106]. Dominantly inherited mutations perturb mitochondrial fusion and damage the mitochondria. Cytoskeletal dynamics, axonal transport, and vesicular motility Mitochondrial fusion and fission Neurons have particularly high energy demands and are especially vulnerable, making the proper functioning of mitochondria essential to peripheral nerve function. As there is no protein synthesis machinery in axons and nerve endings, the transport via microtubules of organelles and proteins needed for survival is essential in neurons [109]. Mtmr2 and Mtmr13 associate to form a complex, leading to increased catalytic activity of Mtmr2 [140]. Endocytosis, intracellular protein sorting, and quality control A defect in the endocytic recycling of proteins or in the quality control system may have an impact on the tightly controlled myelination program in Schwann cells. Specifically, pale tremor mice have a defect in autophagy, which may ultimately lead to neuronal death due to decreased degradation of proteins in neurons [143]. These findings suggest that the degradation of membrane proteins is important for the functioning of cells of the nervous system [133]. Increased expression of the mutant allele rescued this interaction and corrected the autophagy defect [144]. Rab7 is important for growth factor signaling and for regulating endocytosis [148]. Enhanced Trk-A phosphorylation led to increased phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), a signaling pathway downstream from Trk-A, on signaling endosomes. Activated Erk1/2 accumulated in the cytoplasm, which decreased its shuttling to the nucleus where it is needed for up-regulation of genes required for sensory neuron differentiation [148]. It is a membrane protein that regulates protein sorting at the early endosome [153]. Deficits in axonal transport, particularly that of mitochondria, were also found to result from decreased levels of acetylated a-tubulin in an Hspb1 mouse model [165]. The environment may also play a role in modulating disease severity of inherited peripheral neuropathies. Exposure to neurotoxins such as heavy metals and solvents, and medications such as vincristine may also exacerbate disease. These mutant proteins likely cause suboptimal protein quality control through the loss of their chaperone function. The protein, usually translocated from the trans-Golgi network to the plasma membrane as part of its role in copper transport, accumulates at the plasma membrane in mutant cell lines, suggesting impaired endocytic recycling [184]. As discussed previously, mutations in this cation channel often cause increased intracellular calcium and cytotoxicity, and may result from a gain-of-function mechanism [184]. The lack of a functional complex leads to down-regulation of genes related to cell motility, peripheral neurogenesis, and neuronal differentiation, as well as neuronal development and cerebral oligodendrocyte development and myelination [192]. Mutations caused abnormal methylation through decreased enzyme activity and perturbed heterochromatin binding, thus implicating epigenetic mechanisms in neurodegenerative diseases [204]. Although Gan-null mice exhibited relatively mild motor and sensory deficits, they showed severe dysregulation of neurofilaments as in the human neuropathy [210]. The enzyme is necessary for the biosynthesis of sphingolipids, which are components of lipid rafts, structures needed for signal transduction in the plasma membrane. Demyelination may result from a disturbance to the Schwann cell and axon integrity due to immune responses against adhesion molecules located in these structural areas [212]. Identification of biomarkers in peripheral neuropathies As potential drugs are tested in future clinical trials, sensitive outcome measures will become necessary to measure amelioration over time, especially in slowly progressive neuropathies [8]. The development of disease severity markers would assist patients in planning their future with regards to treatment and family planning [8]. Levels of neural protein such as glial fibrillary acidic protein in serum and cerebrospinal fluid are being considered for measuring axonal damage and predicting clinical outcome [216]. Investigations may include blood tests to exclude acquired causes of neuropathy, including a test of glucose tolerance if a diabetic neuropathy is suspected and vitamin assays for nutritional deficiencies. The advent of genetic testing has greatly reduced the need for sural nerve biopsies but biopsy can still be a helpful investigation of acquired and inflammatory neuropathies. Diagnosis of peripheral neuropathies An important part of the assessment of any patient with peripheral neuropathy is a careful history, assessment of acquired risk factors, family tree, and examination. Previously, impairment was measured using the 9-hole peg test, the ambulation index, and a Jamar dynamometer to measure handgrip strength [217]. Investigation of peripheral neuropathies the clinician should first determine whether the neuropathy is motor, sensory and/or autonomic, symmetrical or asymmetrical, chronic or acute, and distal versus proximal. Clues that the neuropathy may be genetic include a positive family history; however, the lack of a positive family history does not necessarily preclude a patient from having a genetic form of neuropathy. Reaching a genetic diagnosis is increasingly important for future treatments targeted to specific causative genes [5, 8]. Treatment options in peripheral neuropathies Unfortunately, no effective treatment currently exists to reverse peripheral nerve damage. In acquired neuropathies, avoiding the cause, improving diabetes control, or treating infection are essential steps for prevention of neuropathy. Alcohol, toxins, or other drugs known to cause neuropathy such as vincristine should be avoided. Neuropathic pain may be relieved by the use of medication such as gabapentin, pregabalin, other anti-epileptics, and/or tricyclic antidepressants. In this case, the use of immunosuppressive or immunomodulatory treatment may be beneficial. Physiotherapy and rehabilitation therapy including stretching, strength training, and gentle exercise to prevent contractures and foot deformities remain extremely valuable in managing the symptoms of neuropathies [221]. Caring for feet, pressure sores, and skin problems that may arise from loss of sensation is also important [224]. Corrective surgery such as osteotomy, arthrodesis, and tendon transfer is used for foot deformities. Patients may benefit from help with everyday and occupational tasks from occupational therapists, as these tasks may be a source of fatigue. Weight control and a healthy diet should also be part of the long-term management of neuropathy patients. Therefore molecules to Future developments in peripheral neuropathies Next-generation sequencing With the development of next-generation sequencing, we expect the diagnosis of inherited neuropathies to be more comprehensive, faster, and cheaper. However, problems with delivery methods and bioavailability may complicate the use of trophic factors in the treatment of neuropathies [221]. Potassium channel blockers to help maintain the charge separation in myelin and the depolarization at the nodes of Ranvier are also being investigated for demyelinating neuropathies, however preliminary trials have not shown any benefit [5]. In the future, treatment options will likely target specific pathogenic mechanisms, making accurate diagnosis even more essential. Gene replacement therapies may be used for loss-of-function or nonsense mutations. Animal models in which a disease-causing gene has been knocked out are becoming increasingly available and will be of great value in further clarifying disease mechanisms and testing molecules for therapeutic treatment. Research is also currently focusing on the use of induced pluripotent stem cells from patients to produce neuronal lines on which to test new therapies [234]. These stem cells may also be used to generate new axons and treat peripheral neuropathies. However, differentiating stem cells into neurons and Schwann cells will likely prove to be a challenge [30]. Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11. New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy. Charcot-Marie-Tooth type 1A appears to arise from recombination at repeat sequences flanking the 1. Inheritance of Charcot-Marie-Tooth disease 1A with rare nonrecurrent genomic rearrangement. Distinct disease mechanisms in peripheral neuropathies due to altered peripheral myelin protein 22 gene dosage or a Pmp22 point mutation. Molecular basis of Charcot-Marie-Tooth disease type 1A: gene dosage as a novel mechanism for a common autosomal dominant condition. Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. Shortened internodal length of dermal myelinated nerve fibres in Charcot-Marie-Tooth disease type 1A. Aberrant protein trafficking in Trembler suggests a disease mechanism for hereditary human peripheral neuropathies. Transport of Trembler-J mutant peripheral myelin protein 22 is blocked in the intermediate compartment and affects the transport of the wild-type protein by direct interaction. Impaired proteasome activity and accumulation of ubiquitinated substrates in a hereditary neuropathy model. Heterozygous peripheral myelin protein 22-deficient mice are affected by a progressive demyelinating tomaculous neuropathy. Evidence for linkage of Charcot-Marie-Tooth neuropathy to the Duffy locus on chromosome 1. Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B. Different intracellular pathomechanisms produce diverse myelin protein zero neuropathies in transgenic mice. Different cellular and molecular mechanisms for early and late-onset myelin protein zero mutations. Mapping of a new locus for autosomal recessive demyelinating Charcot-Marie-Tooth disease to 19q13. Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10. A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. A second locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 19q13. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. A new variant of CharcotMarie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Normal role of the low-molecular-weight neurofilament protein in mitochondrial dynamics and disruption in CharcotMarie-Tooth disease. Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments.

As with all laryngeal carcinomas erectile dysfunction treatment ppt order cialis extra dosage 100 mg line, the presence of cartilaginous invasion or extension into the adjacent soft tissues is very important what causes erectile dysfunction in males purchase cialis extra dosage australia. As stated previously erectile dysfunction what causes it discount cialis extra dosage 40 mg with visa, the risk of lymphatic invasion is much lower with glottic carcinoma diabetes erectile dysfunction wiki order cialis extra dosage american express. Only when the tumor extends to the supraglottis or subglottis is expectant treatment of the lymph nodes required shakeology erectile dysfunction buy generic cialis extra dosage 200 mg line. T1 and T2 glottic carcinomas may be treated with radiation therapy alone in some instances impotence exercises for men cheap 50mg cialis extra dosage with mastercard. The cure rates for T1 glottic carcinoma with either surgery or radiation are approximately 90%. However, the quality of the voice is generally better after focal localized radiation therapy. The radiation therapy usually does not include the lymph node chains because of the sparse lymphatics involved. Subglottic Squamous Cell Carcinoma Subglottic squamous cell carcinomas constitute less than 5% of all laryngeal carcinomas. These lesions are very difficult to identify at indirect or fiberoptic endoscopy because visualization of the undersurface of the vocal cord or the proximal trachea may be obscured by the shadow of apposed true cords. The best views are obtained under supported direct laryngoscopy in the operating room. The staging of subglottic laryngeal carcinoma is similar to that in the glottis and supraglottis and deals primarily with cord mobility, cartilaginous destruction, or extension to the soft tissues of the neck (Box 13-11). The prognosis for subglottic lesions is generally poor because by the time the diagnosis is made, the lesion is generally fairly extensive. The major issue when examining a patient for subglottic carcinoma is whether there is paraglottic, glottic and/ or supraglottic extension at the time of diagnosis. Because surgical resection of subglottic carcinomas nearly always requires cricoid cartilage resection, total laryngectomy is usually performed. T1-Tumor limited to the subglottis T2-Tumor extends vocal cord(s) with normal or impaired mobility T3-Tumor limited to larynx with vocal cord fixation T4a-Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx. Axial T1-weighted imaging demonstrates thickening of the mucosa (arrows) along the left subglottic region. At this level one should not see any thickness to the mucosa of the subglottic larynx. Tracheal carcinomas are much less common than laryngeal carcinomas and enter the realm of pulmonary radiology. The limitations of these studies are predominantly attributable to lower resolution, normal variations in activity, variable uptake shortly after therapy, and the nuclear medicine doctors not having read the anatomy portion of this chapter well enough to challenge "true" neuroradiologists. Chondroradionecrosis One of the most catastrophic of iatrogenic mishaps to affect the larynx is chondroradionecrosis. This may occur in some unusual individuals after standard doses of radiotherapy for laryngeal neoplasms, but is, thankfully, rare to see. Invariably, this entity requires a total laryngectomy, which often was the surgical extreme that the therapists were hoping to avoid by going with radiation therapy for the cancer. Carcinosarcoma A neoplasm that has characteristics of both squamous cell carcinoma and sarcoma is known as the spindle cell sarcoma or carcinosarcoma. This lesion is rarely seen elsewhere in the aerodigestive tract besides the larynx. Its prognosis is similar to that of squamous cell carcinoma in the larynx, and therefore the histologic distinction does not generally alter therapy or prognostic consideration. Radiation therapy in carcinosarcoma produces similar control rates to irradiated patients with similar volume disease with the more typical squamous cell carcinoma. Note the softtissue mass (arrows) along the left thyroid cartilage in this patient with recurrent squamous cell carcinoma. Incidentally, an unusual mucous retention cyst (star) protrudes into the lumen of the larynx. A, After chemoradiation there was still a necrotic mass in the oral tongue and tongue base (arrow) favoring the left side. Chapter 13 Mucosal and Nodal Disease of the Head and Neck 473 Other Mucosal Based Malignancies Lymphoma Squamous cell carcinoma does not have a monopoly on bad news in the nasopharynx. Because of the abundant lymphoid tissue associated with the adenoids of the nasopharynx, lymphoma also occurs here. Its appearance is identical to that of carcinoma except that necrosis is uncommon in lymphoma. Lymphoma in the nasopharynx has the opportunity to spread to the skull base and cranial nerve foramina. Because of the presence of faucial and lingual tonsillar tissue along the tongue base, the incidence of lymphomatous involvement of the oropharynx is significant. Once again these lesions may appear as exophytic masses and can be challenging to distinguish from tonsillar lymphoid hypertrophy. Hodgkin disease rarely affects Waldeyer ring and afflicts adults of younger age than non-Hodgkin lymphoma. Minor Salivary Gland Malignancies the extensive minor salivary gland tissue in the nasopharynx accounts for neoplasms such as adenoid cystic carcinoma (the most common minor salivary gland malignancy), mucoepidermoid carcinoma, acinic cell carcinoma, adenocarcinoma, pleomorphic low-grade adenocarcinoma, and undifferentiated carcinoma. Adenoid cystic carcinomas may be particularly difficult to treat because of their tendency to spread perineurally (seen in 60% of individuals). The skull base foramina are easy targets for nasopharyngeal adenoid cystic carcinomas, and from there the tumor marches up the nerves to the intracranial compartment. Perineural progression portends a poor prognosis and potentially produces partial paresis plus paresthesia. Nearly half of minor salivary gland tumors of the oropharynx are pleomorphic adenomas with the other half being malignant. Minor salivary gland malignancies of the oropharynx are usually due to adenoid cystic carcinoma. It is nearly impossible to distinguish among the major histologic types of noncarcinomatous tumors that involve the nasopharynx. Age is probably the best discriminator, with lymphomas occurring more commonly in the young adult. Lymphoma frequently has a homogeneous bland appearance even when the tumor is large. Its signal intensity may be variable but usually is indistinguishable from that of nonnecrotic carcinoma. Lymphoma often grows in a more exophytic pattern, with less deep infiltration than carcinoma. Plasmacytomas Plasmacytomas can occur in the nasopharynx, palatine tonsils, and base of tongue. Intracranial extension is common with rhabdomyosarcomas, and rhinorrhea may be a presenting symptom. Of the tumors of the nasopharynx that may be hemorrhagic, rhabdomyosarcoma is the most common. Rhabdomyosarcoma rapidly races retropharyngeally requiring a referral for radiotherapy. The survival rate with combined chemotherapy and radiation is more than 50% at 5 years. Also in the sarcomatous category, hemangiopericytomas and synovial sarcomas may occur in the oropharynx. The malignancies other than squamous cell carcinoma that affect the vocal cords include the chondroid tumors. A, Loss of the anterior portions of the thyroid cartilage bilaterally is coupled with extralaryngeal air in the preglottic and paraglottic soft tissues (arrowheads). B, At the cricoid level the necrotic tissue (arrows) is seen projecting anteriorly into the strap muscles. Distinguishing a benign from a malignant chondroid tumor is sometimes difficult; in the larynx the chondrosarcomas are usually low-grade and slow growers. Chondrosarcomas account for less than 1% of laryngeal malignancies, are seen in the 40 to 60 age range and predilect males by 5 to 10 to 1. A well-defined yet heterogeneous mass with septations, hemorrhage, cysts, calcification, or multilocularity should raise suspicion of a synovial sarcoma. Saying "synovial sarcoma" should not suggest a synovial source, simply cell shape. Note how homogeneous this oropharyngeal lymphoma (L) is affecting the palatine tonsil and spilling into the parapharyngeal, masticator, carotid, and retropharyngeal spaces. Although the lymph nodes are not strictly a part of the mucosal system of the head and neck, it seems more relevant to discuss the nodes in the chapter dealing with squamous cell carcinoma. The most common cause of nodal disease in an adult is a squamous cell carcinoma metastasis from a mucosal primary tumor. Chapter 13 Mucosal and Nodal Disease of the Head and Neck 475 the nomenclature of the lymph nodes of the neck has undergone a recent change, which is supported by various societies of head and neck surgeons. Lifelong labor in learning levels of lymph nodes leads to learned lymphatic luminaries. Level I lymph nodes include the submental (Ia) and submandibular (Ib) lymph node chains. Level V is designated as all the lymph nodes of the posterior triangle of the neck (deep and posterior to the sternocleidomastoid muscle and above the clavicle). The critical numbers to remember are less than or equal to 3 cm for N1 nodes, 3 to 6 cm for N2 lymph nodes, and greater than 6 cm for the N3 classification. Note the cricoid origin (arrow), popcorn-like appearance with whorly matrix that characterize this tumor. The nodal staging for the nasopharynx is "special"; N0 no nodes, N1 unilateral supraclavicular node 6 cm or less, N2 bilateral supraclavicular nodes 6 cm or less, and N3 nodes greater than 6 cm or into the supraclavicular region. Issues other than pure size criteria include the presence (or absence) of central nodal necrosis, which suggests tumor no matter what the size. Any adenopathy Bilateral adenopathy Extracapsular spread of tumor Fixation to vital structures. The numbers argue that even in the best of hands, over 20% of patients with N0 necks clinically have occult nodal metastases. Of the positive specimens from neck dissections of N0 patients (around 30% of cases), 25% reveal metastases less than 3 mm in size. Some lymph nodes that are located deep in the head and neck are not clinically palpable. Sometimes,deep parapharyngeal lymph nodes and/or lymph nodes in the jugular digastric chain (level 2) may not be readily palpable. For this reason it is generally accepted that 15% to 30% of all malignant lymph nodes escape clinical detection. The role of the radiologist is to identify these lymph nodes and the very small lymph nodes that demonstrate central nodal necrosis that may be dismissed by the clinician (and unsophisticated radiologist) as insignificant. A, Fat-suppressed, enhanced T1-weighted imaging readily depicts the spread of neoplasm from the lymph node (n) into the soft tissues of the neck. The presence of extracapsular spread portends a worse prognosis and problems obtaining "clean margins" at surgery. Axial T2-weighted image shows a bulky pharyngeal mass (yup, you guessed it, squamous cell carcinoma), clearly visible on endoscopy. Chapter 13 Mucosal and Nodal Disease of the Head and Neck 477 infiltrated with neoplasm. The debate centers on millimeters, some favoring 10 mm, some 12 mm, and some 15 mm as the maximum normal transverse diameter of a reactive node. Most would agree that at greater than 15 mm (longest measurement in the axial plane) the node should be considered suspicious until proved otherwise. In many cases, whether we say there are nodes or not, the surgeons go ahead and treat the necks. They know that some primary tumors, such as oropharyngeal, hypopharyngeal, and supraglottic cancers have such a high rate of nodal involvement (in the 60% range) that they are simply going to treat regardless of what they feel, you see, and Aunt Minnie wants. Furthermore, they tend to take out the nodes because it affords them better access to the primary tumor with that fatty nodal stuff removed. They realize that the incidence of malignant cervical lymphadenopathy with squamous cell carcinoma varies with the primary tumor from site to site (Table 13-9). If you combine a short axis diameter of 5 to 7 mm with absence of hilar blood flow, the sensitivity can rise to near 90% and specificity to around 95%. This technique is very accurate (with a specificity approaching 99%) but requires the patience and expertise that many Americans do not possess. The shape of the lymph node may also be a secondary indication of whether it is involved by tumor. More rounded lymph nodes have a greater chance of being neoplastic than those which have a kidney bean shape. Most authors agree that a lymph node that has central necrosis no matter what its size should be considered malignant until proved otherwise, unless the patient has active tuberculosis or has been treated with radiation in the past for lymphoma. A lymph node with fat centrally is benign and may signify previous inflammation and/or radiation. Heterogeneous contrast enhancement, calcifications, asymmetric clustering, and perinodal stranding should help improve your odds in detecting malignant adenopathy. Having a lymph node with your primary tumor cuts your 5-year prognosis by 50%, having bilateral nodes cuts it another 50%, having extracapsular spread of tumor cuts it another 50%, having fixation to vital structures (carotids, vertebral arteries, paraspinal muscles, transverse processes, brachial plexi) cuts it another 50%, and 50% of our school age children have lymph nodes palpable 50% of the time. Malignant Adenopathy: Other Considerations Another important issue to consider when you are dealing with internal jugular chain lymph nodes is the presence or absence of carotid invasion by lymphadenopathy. Presently, no ideal radiographic study can predict whether the carotid artery is invaded by tumor when there is contiguous lymphadenopathy. It has generally been accepted that if less than 270 degrees of the circumference of the carotid artery is encircled by squamous cell carcinoma, the likelihood of carotid wall invasion is small.

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