In the group in which the abnormalities are confined to the nervous system, attention is focused on a larger number of diseases, many due to exogenous factors such as perinatal hypoxia-ischemia, pre- or postnatal infections, trauma, and so on. The degree of mental retardation is variable, depending on the location and extent of a demonstrable neuropathology. Usually the family history is negative, but careful questioning of parents regarding the pregnancy, delivery, and early postnatal period and examination of hospital records from birth may disclose the nature of the neurologic insult. The third category of retardates is one in which neither somatic anomalies nor focal neurologic signs are present, or they are minimal. The more severely retarded of this special group are represented by the following disease states: autism (Asperger-Kanner syndrome), the Rett and Williams syndromes, and the fragile X and Renpenning syndromes. All of these but autism are now known to have a genetic basis, as noted earlier in the chapter, and are described together below. The practical importance of this clinical approach is that it directs the intelligent use of laboratory procedures for confirmation of the diagnosis. Karyotyping and genetic studies are useful in group 1 and rarely in group 2 patients. The major pitfall to be avoided in this clinical approach is in mistaking a hereditary metabolic disease for a developmental one. Here one is helped by the fact that manifestations of the metabolic diseases are not usually present in the first days of life; they appear later and are progressive and often associated with visceral abnormalities. However, some metabolic diseases are of such slow progression that they appear almost stable, especially the late-onset ones, such as one type of metachromatic leukodystrophy, late-onset Krabbe leukodystrophy, adult adrenoleukodystrophy, and adult hexosaminidase deficiency (see Chap. Differentiation of Types of Retardation: Clinical Approach As a particular guide to the pediatrician and neurologist who must assume responsibility for the diagnosis and management of backward children harboring a wide array of diseases and maldevelopments of the nervous system, the following clinical approach is suggested. First, as already described, there is an advantage in setting aside as one large group those who are only mildly retarded from those who have been severely delayed in psychomotor development since early life. With regard to the former group, having no obvious neurologic signs or physical stigmata, one should nevertheless initiate a search for the common metabolic, chromosomal, and infective diseases. In this large group one must be sure that their deficit is a general one and not one of hearing, poor sight, or the special isolated language and attention deficits described in Chaps. For patients with moderately severe and very severe cognitive deficits, one begins with a careful physical examination, searching specifically for somatic stigmata and neurologic signs. Abnormalities of eyes, nose, lips, ears, fingers, and toes are particularly important, as are head circumference and a variety of neurologic ab- Hereditary Mental Retardations Fragile X Syndrome (See page 864) Great interest has been evinced in this syndrome, which some geneticists hold accountable, at least in part, for the preponderance of males among institutionalized retarded individuals. At first, it was assumed that the fragile X syndrome was only an example of the Renpenning syndrome (an X-linked hereditary mental retardation in males- see below), until it was pointed out that in this latter condition, stature was reduced, as was the cranial circumference, and further that the X chromosomes of the Renpenning patients were normal. In some series, fully 10 percent of mentally retarded males have this fragile X chromosomal abnormality, although 2 to 4 percent is more accurate according to others. Females are sometimes affected, but their mental function is only slightly reduced. Affected males have only mild dysmorphic features (large ears, broad forehead, elongated face, and enlarged testes) that may not become obvious until puberty. Pulsifer, whose review of the neuropsychologic aspects of mental retardation is recommended, lists self-injurious, hyperactive, and impulsive behaviors as the most common. Rett Syndrome (See page 965) this is yet another hereditary form of mental retardation, but affecting girls. The responsible spontaneous mutation has been shown to relate to a defect at chromosomal site Xq28, making it one of the X-linked mental retardations. A fatal outcome in boys due to a severe neonatal encephalopthy explains the expression of the disease only in girls, who are mosaics for the mutation. Defective function of the gene leads to an alteration in synaptogenesis and neural connectivity (Neul and Zoghbi). Severe inactivation of gene expression causes classic Rett syndrome, but it has become apparent that incomplete expression and mosacism lead to a number of partial syndromes, including nonspecific mental retardation, tremor, psychiatric disturbances, and autism-like presentations. Prevalence studies from Sweden indicate an occurrence of 1 per 10,000 girls; thus Rett syndrome is more common than phenylketonuria.
Submit the completed form and supporting documentation as outlined in the protocol. Information on drug formulation, procurement, storage and accountability, administration, and potential toxicities are outlined in section 7. The aim has always been to focus on the creative and production energies to create a unique and strong corporate identity. Our real estate is not just the industrial property, but also the intellectual assets of men who have been working with us for over 30 years. In the R&D department our specialists process the inputs from the users in order to develop new products, improve existing ones and make them all unique products that stand out from those of our competitors. Each piece of equipment is supplied with a testing certificate in compliance with current regulations. Each division has a dedicated workgroup which aims at offering ever innovative solutions and high-tech devices in line with corporate values and mission. A new treatment method for pain relief in acute and chronic phase, and against diabetic neuropathy. The products developed in Kieme have been specially designed to be used in synergy with the aesthetic and aesthetic medicine equipment, in order to achieve better and long lasting effects. By registering the equipment to our reserved area, its warranty will automatically be extended of 6 months for a total of 30 months. Our Physio-specialists will clarify all the doubts that might appear regarding our technologies and how to use them when treating patients. The EleKta line supports the professional in their work, guiding them step by step to deliver the best treatment providing on display useful information on it. They pass through the skin surface and spread in a radial way through the body in the painful area. The shockwave is generated in a special gun-shaped applicator: a steel bullet is shot against a metallic lid inside the barrel of the applicator by means of compressed air (pressure up to 5 bar). This process generates a shockwave that spreads in a radial way through the skin and the first tissue layer under it or in a focused way (depending on the transmitter used). The body responds by increasing metabolic activity in the area being treated and this helps to reduce the inflammation caused by the pain-killing action of released local endorphin. Main application fields: - Orthopedics - Physical rehabilitation - Sport medicine - Aesthetic medicine Made in Italy Shock med Available models the smart shockwave therapy Wide display: 8" colour touch-screen. It stimulates from the inside the biological structures (tendons, muscles, joints) and natural reparative and anti-inflammatory processes of the human body. By the interaction between electro-magnetic energy and tissue, diathermy causes the temperature inside the tissues to increase in a controlled uniform way. There are different types of electrodes: resistive type electrodes: the treatment is delivered through a resistive (non isolated) electrode that moves the charges and concentrates them in the deeper areas with a greater resistance (bone matrix and deep muscles). The biological effect is obtained in the tissues with a higher resistance interposed between the mobile electrode and the return plate, that is bones, joins, tendons, ligaments and cartilages. It acts on soft tissues, rich in water, such as muscles, the lymphatic system etc. The light beam delivered by Crystal Yag can be regulated up to a maximum power of 25W, which has a high value of tissue penetration. Its effects provide photo-chemical bio-stimulations on the cellular membrane and inside the mitochondrions, acting in depth in the tissues and inducing significant effects of metabolic, analgesic, antioedema, antiphlogistic stimulation. With Crystal Yag you can treat safely all muscle-skeletal inflammatory conditions, both superficial and in depth, inducing already in the first session a decrease in pain and mobility recovery. This system makes the biostimulation effect of tissue more effective and significant. Bipower Lux is recommended for superficial pathologies in general medicine and dermatology and for orthopaedic and sport medicine pathologies (contusions, bursitis, tendinitis, etc.
Primer for Emergency Medicine Students A first-degree strain is a minor tearing of the musculotendinous unit, characterized by spasm, swelling, local tenderness, and minor loss of function. Findings increase along a continuum such that in a seconddegree strain more fibers are torn but without complete disruption; swelling, ecchymosis, muscle spasm, and loss of strength are more marked. In a third-degree strain the muscle or tendon is completely disrupted, with resultant separation of muscle from muscle, muscle from tendon, or tendon from bone. Assessment: Signs and symptoms include marked pain and spasm, ecchymosis, swelling, and loss of function. A force applied to the muscle will produce sharp pain at the site of injury; a palpable defect is frequently present at the site of rupture as well. Sometimes a bunching up of the muscle may be appreciated, as is typically seen in a biceps muscle rupture. In the non-athlete, strains usually present in patients that have over-stressed a muscle group or who have tried to generate excessive force in a cold or non-conditioned muscle. Examples are the weekend gardener or mover who presents on Monday morning with lower back strain, the aerobics student who strains the rectus muscle, and the novice weight lifter who presents with chest wall pain secondary to pectoral strain. Rapid acceleration in a tennis player, for instance, may result in a third-degree gastrocnemius tear, just as pushing off to jump often ruptures the Achilles tendon in the basketball player. Not infrequently the sudden violent attempt at lifting in the older individual results in a complete biceps disruption. Sudden generation of the tremendous forces of which the thighs are capable frequently results in second-degree strain of the thigh adductors, hamstrings, or quadriceps muscles. In the athlete, generation of tremendous contraction forces coupled with excessive forcible stretching (while the body may be either accelerating or "planting") results in severe strains. Involvement of almost any muscle group is possible, and the onset of such injuries is usually acute. Immediate removal from activity, application of ice, and rest are mandatory to prevent further injury. Treatment and Disposition: Treatment will depend on the degree of disruption, the location, and the functional loss. Second-degree strains are treated similarly, with immobilization of the affected part required for longer periods. Passive stretching during the early days post-injury will impede healing and may result in fibrosis or calcium deposition in injured muscle. For patients with significant lower back injuries and in competitive athletes, a physical therapist may help in the rehabilitation process. Thirddegree strains are treated similarly in the emergency department, along with early orthopedic consultation. Some of these injuries are amenable to surgical repair whereas others may be treated with immobilization. The muscle affected, the age of the patient, occupation, and activity level are all factors in deciding on whether surgical intervention is appropriate. Proper training, warm-up and stretching exercises, and avoidance of overexertion can accomplish prevention of many strains. Emergency personnel themselves should seek to avoid these injuries in the course of their demanding work, especially during patient transfers. Tendonitis Tendinitis is an inflammatory condition characterized by pain at tendinous insertions into bone; it is frequently the result of overuse. In some locations, particularly the shoulder, chronic irritation results in calcium deposition along the course of the tendon; when present, the painful condition that ensues is termed calcific tendinitis. Primer for Emergency Medicine Students Physical examination typically presents with pain on motion and limitation of function. Point tenderness and palpable crepitus over the involved tendon with motion is generally present. In general, a clinical test can be performed by forcible flexion of the involved muscle while keeping the point of insertion fixed, or by operating the involved muscle against resistance. A small fleck of bone may suggest an avulsion, or the surface of the bone at the attachment may be roughened, indicating periostitis.
A muscle biopsy may disclose several basic abnormalities; ragged red fibers can be recognized by use of the modified Gomori stain on frozen material, and the absence of succinate dehydrogenase and cytochrome oxidase by appropriate histochemical staining. It should be evident from the foregoing discussion that normal findings in any of these tests, including the muscle biopsy, do not exclude mitochondrial disease. In the final analysis, it is the clinical syndrome, family history, and any corroborating evidence of a mitochondrial disorder or its genetic representation that is diagnostic. Jackson and coworkers suggest that isolated phenomena such as dementia, muscle weakness, epilepsy, nerve deafness, migraine with strokes, small stature, myoclonic epilepsy, or cardiomyopathy should prompt consideration of a mitochondrial disorder when no other explanation is evident. They number in the hundreds, according to the tabulation of Dyken and Krawiecki, although many are very rare. The first includes many unrelated genetic pathologic processes: some stem from germplasm abnormalities; others are associated with triplication, deletion, and translocations of chromosomes; and probably some are inherited on a polygenic basis. A remarkable accomplishment has been the identification in the past several years of specific gene defects that give rise to malformations of the brain. The second category is composed of the effects of a variety of noxious agents acting at different times on the immature nervous system, i. It would be intellectually satisfying if all the states that originate in the intrauterine period could be separated strictly into genetic (hereditary) or nongenetic forms, but in many instances the biologic information and the pathologic changes in the brain at this early age do not allow such a division. For example, among the many diseases in which the neural tube fails to close (rachischisis), more than one member of a family may be affected; but it cannot be stated whether a genetic factor is operative or an exogenous factor, such as folic acid deficiency, has acted on several members during a succession of pregnancies of one mother. Even what appears to be an outright malformation of the brain may be no more than a reflection of the timing of an exogenous process that has affected the nervous system and other organs early in the embryonal period, derailing later processes of development. Teratology, the scientific study of neurosomatic malformations, is replete with such examples. Several points should be noted regarding the frequency of developmental disorders. Jones) points out that a single malformation, usually of no clinical significance, occurs in 14 percent of newborns. The figures for major congenital malformations, compiled by Kalter and Warkany, are somewhat higher. What is most important for the neurologist is the fact that the nervous system is involved in most of these infants with major malformations. A perusal of the following pages makes it evident that there is a great variety of structural defects of the nervous system in early life; in fact, every part of the brain, spinal cord, nerves, and musculature may be affected. Furthermore, certain principles are applicable to the entire group of developmental brain disorders. First, the abnormality of the nervous system is frequently accompanied by an abnormality of some other structure or organ (eye, nose, 850 cranium, spine, ear, and heart), which relates them chronologically to a certain period of embryogenesis. Conversely, the presence of these malformations of nonnervous tissues suggests that an associated abnormality of the nervous system is developmental in nature. This principle is not inviolable; in certain maldevelopments of the brain, which must have originated in the embryonal period, all other organs are normal. One can only assume that in this instance the brain was more vulnerable than any other organ to prenatal as well as natal influences. Perhaps this occurs because the nervous system, of all organ systems, requires the longest time for its development and maturation, during which it is susceptible to disease. Second, a maldevelopment of whatever cause should be present at birth and remain stable thereafter, i. Again, this principle requires qualification- the abnormality may have affected parts of the brain that are not functional at birth, so that an interval of time must elapse postnatally before the defect can express itself. Third, for an abnormality to be characterized as developmental, birth should have been nontraumatic and the pregnancy uncomplicated by infection or other injurious event. Conversely, the occurrence of a traumatic birth is not proof of a causative relationship between the injury (or infection) and the abnormality, because a defective nervous system may itself interfere with the birth or the gestational process. Fourth, if the congenital abnormality has occurred in other members of the family of the same or previous generations, it is usually genetic- although, as noted above, this does not exclude the possible adverse effects of exogenous agents.
Diseases
Simply engaging the patient in conversation permits assessment of the motor aspects of speech (praxis and prosody), fluency, and language formulation. Impaired comprehension but perfectly normal formulated speech and intact ability to read suggest the rare syndrome of pure worddeafness. When conversation discloses virtually no abnormalities, other tests may still be revealing. Reading aloud single letters, words, and text may disclose the dissociative syndrome of pure word-blindness. Except for this syndrome and pure word mutism (see above), writing is disturbed in all forms of aphasia. Similar errors appear even more frequently when the patient is asked to explain the text, read aloud, or give an explanation in writing. As with other tests of aphasia, it may be necessary to increase the complexity of the test- from digits and simple words to complex words, phrases, and sentences- in order to disclose the full disability. The patient may be unable to repeat what is said to him, despite relatively adequate comprehension- the hallmark of conduction aphasia. Contrariwise, normal repetition in an aphasic patient (transcortical aphasia) indicates that the perisylvian area is largely intact. Preserved repetition is also characteristic of anomic aphasia and occurs occasionally with subcortical lesions. Disorders confined to naming, other language functions (reading, writing, spelling, etc. These deficits can be quantified by the use of any one of several examination procedures. The use of these procedures will enable one to predict the type and localization of the lesion in approximately twothirds of the patients, which is not much better than detailed bedside examination. Using these tests, aphasia of the Broca, Wernicke, conduction, global, and anomic types accounted for 392 of 444 unselected cases studied by Benson. Treatment the sudden onset of aphasia would be expected to cause great apprehension, but except for cases of pure or almost pure motor disorders of speech, most patients show remarkably little concern. It appears that the very lesion that deprives them of speech also causes at least a partial loss of insight into their own disability. Reassurance and a program of speech rehabilitation are the best ways of helping the patient at this stage. Whether contemporary methods of speech therapy accomplish more than can be accounted for by spontaneous recovery is still uncertain. Most aphasic disorders are due to vascular disease and trauma, and they are nearly always accompanied by some degree of spontaneous improvement in the days, weeks, and months that follow the stroke or accident. A Veterans Administration Cooperative Study (Wertz et al) has suggested that intensive therapy by a speech pathologist does hasten improvement. Also, Howard and colleagues have shown increased efficacy of word retrieval in a group of chronic stable aphasics treated by two different techniques. In an interesting personal experiment by Wender, a classicist who had become aphasic, practice of Greek vocabulary and grammar led to recovery in that language, but there was little recovery of her facility with Latin, which was not similarly exercised. As a rule, therapy is not advisable in the first few days of an aphasic illness, because one does not know how severe or lasting it will be. Also, if the patient suffers a severe global aphasia and can neither speak nor understand spoken and written words, the speech therapist is virtually helpless. Under such circumstances, one does well to wait a few weeks until one of the language functions has begun to return. Then the physician and therapist can begin to help the patient to use that function to a maximum degree. In milder aphasic disorders, the patient may be sent to the speech therapist as soon as the illness has stabilized. The methods of language rehabilitation are specialized, and it is advisable to call in a person who has been trained in this field. Frustration, depression, and paranoia, which complicate some aphasias, may require psychiatric evaluation and treatment. The developmental language disorders of children pose special problems and are considered in Chap.
The sensory nerve fibers vary greatly in size and in the thickness of their myelin covering; based on these dimensions, they are classified as type A, B, or C as discussed in Chap. The ventral, or anterior (efferent, or motor), roots are composed of the emerging axons of anterior and lateral horn cells and motor nuclei of the brainstem. Large, heavily myelinated fibers terminate on muscle fibers and smaller unmyelinated ones terminate in sympathetic or parasympathetic ganglia. From these autonomic ganglia issue the axons that terminate in smooth muscle, heart muscle, and glands. The vast extent of the peripheral ramifications of cranial and spinal nerves is noteworthy, as are their thick protective and supporting sheaths of perineurium and epineurium and their unique vascular supply through longitudinal arrays of richly anastomosing nutrient arterial branches that run in the epineurium and perineurium. The perineurium comprises the connective tissue sheaths that surround and separate each bundle of nerve fibers (fascicles) of varying size, each fascicle containing several hundred axons. The sheath that binds and surrounds all the fascicles of the nerve is the epineurium. As the nerve root approaches the cord, the epineurium blends with the dura (see. The fine connective tissue covering of individual nerve fibers is the endoneurium. The nerves traverse narrow foramina (intervertebral and cranial) and a few pass through tight channels peripherally in the limbs. These anatomic features explain the susceptibility of certain nerves to compression and entrapment and also to ischemic damage. The axons themselves contain a complex internal microtubular apparatus for maintaining the integrity of their membranes and for transporting substances such as neurotransmitters over long distances between the nerve cell body and the distant reaches of the nerve fiber. Nerve fibers (axons) are coated with short segments of myelin of variable length (250 to 1000 m), each of which is enveloped by a Schwann cell and its membrane. Each myelin segment and Schwann cell has a symbiotic relationship to the axon but is always morphologically independent. The structure of the axonal membrane in the gaps between segments of the myelin sheaths (nodes of Ranvier) is specialized, containing a high concentration of sodium channels and permitting the saltatory electrical conduction of nerve impulses, as described in Chap. Unmyelinated fibers, more numerous in peripheral nerves than myelinated ones, also arise from cells in dorsal root and autonomic ganglia. Small bundles of these naked (unmyelinated) axons are enveloped by a single Schwann cell; delicate tongues of Schwann cell cytoplasm partition these bundles and separate individual axons. Each sensory nerve fiber terminates in a specialized ending which is designed to be especially sensitive to certain natural stimuli as discussed in Chaps. Diagram showing the relationships of the peripheral nerve sheaths to the merather than fibroblasts. Disease of the connective tissues may subarachnoid angle, the arachnoid is reflected over the roots and becomes continuous with the affect the peripheral nerves that lie within their outer layers of the root sheath. A subset of these is characterized by the and motor nerves via sulfhydryl bonds; and vincristine toxicity, binding of circulating antibodies to the specialized regions at the which damages the microtubular transport system. Also, a atomic pathways are probably implicated in other diseases by complement-dependent, humoral immune reaction against the radmechanisms that remain to be discovered. Toxic or immunologic agents Among the genetically determined neuropathies, the altered that selectively damage the Schwann cells or their membranes, gene products are now known in some cases to lead to defective cause demyelination of peripheral nerves leaving axons relatively myelination, which greatly slows conduction along nerves. In other intact, or a toxin may specifically affect axons by poisoning their genetic diseases it is speculated that structural components of the cell bodies, the axolemma, or the lengthy and complex axonal axon are disrupted, leading to axonal degeneration and impaired transport apparatus. Pathologic Reactions of Peripheral Some of this is theoretical and somewhat speculative. At Nerve present we can cite only a few examples of diseases or toxins that cause disease through these mechanisms exclusively. The classic ones of motor and sensory nerves (the most vascular parts of the peare segmental demyelination, wallerian degeneration, and axonal ripheral nerve); polyarteritis nodosa, which causes widespread ocdegeneration (diagrammatically illustrated in. In wallerian degeneration, there is degeneration of the axis cylinder and myelin distal to the site of axonal interruption (arrow), and central chromatolysis.
If the patient experiences recurrent isolated drug fever following pre-medication and post-dosing with an appropriate antipyretic, the infusion rate for subsequent dosing should be 50% of the previous rate. The first time a patient experiences a grade 3 acne/acneiform rash associated with pain, disfigurement, ulceration, or desquamation, cetuximab therapy is to be held for up to four consecutive infusions with no change in the dose level. The Investigator also can consider concomitant treatment with topical and/or oral antibiotics; topical corticosteroids are not recommended. If the toxicity resolves to Grade 2 or less by the following treatment period, treatment may resume. With subsequent occurrences of a Grade 3 acne/acneiform rash, cetuximab therapy again may be omitted for up to four consecutive weeks. Treatment may resume with reduced dose of cetuximab if skin toxicity has resolved to Grade 2 or less. Cetuximab will be discontinued if there are more than 4 consecutive infusions held or if there is a subsequent occurrence of a fourth episode of Grade 3 acne-like rash (rash/desquamation). If cetuximab is omitted for more than four consecutive infusions for toxicity due to cetuximab, patients should be discontinued from further cetuximab. Dose Modifications During Concurrent Therapy (3/4/10) Paclitaxel/Carboplatin/Cetuximab Dose Modifications for Hematologic Toxicity Paclitaxel Dose At Start of Subsequent Cycles of Therapy a Maintain dose level Maintain dose level Hold therapyB Hold therapyB Hold therapyB Carboplatin Dose at Start of Subsequent Cycles of Therapy a Maintain dose level Maintain dose level Hold therapyB Hold therapyB Hold therapyB Cetuximab Dose at Start of Subsequent Cycles of Therapy a Maintain dose level Maintain dose level Hold therapyB Hold therapyB Hold therapyB 7. Doses that are missed during weekly schedule concurrent with radiation will not be made up but will be documented. Radiation therapy will be held for grade 4 toxicities hematologic described in the table above. With the exception of allergic/hypersensitivity or cytokine release reaction (see Sections 7. Radiation therapy should continued to be delivered for Grade 3 non-hematologic toxicities in or outside the radiation treatment field. In any case of cetuximab treatment delay, there will be no reloading infusion, and all subsequent treatments will be at the current dose level. Carboplatin Dose Modifications for Renal Toxicity (9/22/09) A > 10% change in the serum creatinine, based on weekly calculated creatinine clearance, will warrant a recalculation of the carboplatin dose (see Section 7. If there is a decline in Zubrod performance status to 2 for greater than 2 weeks while under treatment, radiotherapy should be held with no further chemotherapy administered. On day of chemotherapy administration during any treatment week, omit paclitaxel and carboplatin until toxicity resolves to grade 2 as detailed in the table above. If treatment is interrupted for > 2 weeks, protocol treatment should be discontinued. If not, decrease by 1 dose by 1 dose level when 1,500 mm3 level when 1,500 mm3 b Hold therapyb. If not, decrease by 1 dose by 1 dose level when level when 1,500 mm3 1,500 mm3 Hold therapyb and decrease by 1 dose level when 1,500 mm3 Maintain dose level 4 (< 500/mm3) Neutropenic fever Hold therapyb and decrease by 1 dose level when 1,500 mm3 Maintain dose level, unless reoccurs after discontinuation of paclitaxel and carboplatin, then decrease by 1 dose level Maintain dose level Hold therapyb and decrease by 1 dose level unless reoccurs after discontinuation of when 1,500 mm3 paclitaxel and carboplatin, then decrease by 1 dose level Maintain dose level Hold therapyb and decrease by 1 dose level unless reoccurs after discontinuation of when 1,500 mm3 paclitaxel and carboplatin, then decrease by 1 dose level Thrombocytopenia 1 (75,000/mm3) 2 (50,000 - 74,999/ mm3) 3 (25,000- 49,999/ mm3) 4 (< 25,000/mm3) a Other Hematologic toxicities Maintain dose level Maintain dose level Maintain dose level Hold therapyb. Maintain Maintain dose level dose level if fully recovered dose level if fully in 1 week. If not, decrease by 1 dose by 1 dose level when 75,000 mm3 level when 75,000 mm3 b Hold therapy. Maintain Maintain dose level unless reoccurs after dose level if fully recovered dose level if fully in 1 week. If discontinuation of not, decrease by 1 dose paclitaxel and by 1 dose level when carboplatin, then 75,000 mm3 level when 75,000 decrease by 1 dose level mm3 Maintain dose level Hold therapyb and Hold therapyb and decrease by 1 dose level decrease by 1 dose level unless reoccurs after discontinuation of when 75,000 mm3 when 75,000 mm3 paclitaxel and carboplatin, then decrease by 1 dose level There will be no dose modifications for changes in leukopenia or lymphopenia. When a chemotherapy dose reduction is required during the consolidation course of therapy, re-escalation of the chemotherapy dose will not be allowed for subsequent doses during that specific course. In any case of cetuximab treatment delay, there will be no reloading infusion, and all subsequent treatments will be at the current level. Carboplatin Dose Modifications for Renal Toxicity (9/22/09) A > 10% change in the serum creatinine, based on weekly calculated creatinine clearance, will warrant a recalculation of the carboplatin dose. Paclitaxel Dose Modifications for Neuropathy If paclitaxel doses must be withheld for greater than two consecutive weeks, the drug will be held permanently for the duration of consolidation therapy. A delay in protocol treatment of greater than 15 days during the concurrent phase and more than 4 weeks in the consolidation phase.
The condition raises questions of recurrent tumor or the development of a local sarcoma, but the absence of a mass lesion and of pain, and the signs on neurologic examination are most consistent with a regional fibrosing plexopathy or neuropathy. Examples that we have seen are multiple cranial neuropathies after radiation of nasopharyngeal tumors, cervical and especially brachial neuropathies after laryngeal and breast cancers, and lumbosacral plexopathies and cauda equina damage with pelvic radiation. Treatment and Prevention It must be kept in mind that radiation myelopathy is an iatrogenic disease and is therefore largely preventable. The tolerance of the adult human spinal cord to radiation- taking into account the volume of tissue irradiated, the duration of the irradiation, and the total dose- has been determined by Kagan and colleagues. These authors reviewed all of the cases in the literature up to 1980 and concluded that radiation injury could be avoided if the total dose was kept below 6000 cGy and was given over a period of 30 to 70 days, provided that each daily fraction did not exceed 200 cGy and the weekly dose was not in excess of 900 cGy. It is noteworthy that in the cases reported by Sanyal and associates, the amount of radiation surpassed these limits. Forewarned with this knowledge, radiation specialists have the impression that the incidence of this complication is decreasing. A number of case reports remark on temporary improvement in neurologic function after the administration of corticosteroids. This therapy should be tried, because in some patients it appears to arrest the process short of complete destruction of all sensory and motor tracts. Claims have also been made of regression of early symptoms in response to the administration of heparin split products or hyperbaric oxygen, neither confirmed. Spinal Cord Injury due to Electric Currents and Lightning Among acute physical injuries to the spinal cord, those due to electric currents and lightning, despite their rarity, are of interest because of their unique clinical characteristics. Electrical Injuries In the United States, inadvertent contact with an electric current causes about 1000 deaths annually and many more nonfatal but serious injuries. About one-third of the fatal accidents result from contact with household currents. The factor that governs the damage to the nervous system is the amount of current, or amperage, with which the victim has contact, not simply the voltage, as is generally believed. In any particular case, the duration of contact with the current and the resistance offered by the skin (this is greatly reduced if the skin is moist or a body part is immersed in water) are of critical importance. The physics of electrical injuries is much more complex than these brief remarks indicate (for a full discussion, see the reviews by Panse and by Winkelman). Any part of the peripheral or central nervous system may be injured by electric currents and lightning. The immediate effects are apparently the result of direct heating of the nervous tissue, but the pathogenesis of the delayed effects is not well understood. They have been attributed to vascular occlusive changes induced by the electric current, a mechanism proposed to underlie the delayed effects of radiation therapy (see earlier). However, the latent period is measured in many months or a few years rather than in days and the course is more often progressive than self-limited. Moreover, the few postmortem studies of myelopathy due to electrical injury have disclosed a widespread demyelination of long tracts, to the point of tissue necrosis in some segments, and relative sparing of the gray matter, but no abnormalities of the blood vessels. The syndrome of focal muscular atrophy occurring with a delay of weeks to years after an electric shock has been described by Panse under the title of spinal atrophic paralysis. It occurs when the path of the current, usually of low voltage, is from arm to arm (across the cervical cord) or arm to leg. Pain and paresthesias occur immediately in the involved limb but these symptoms are transient. Mild weakness, also unilateral, is immediate, followed in several weeks or months by muscle wasting, most often taking the form of segmental muscular atrophy. Occasionally the syndrome simulates that of amyotrophic lateral sclerosis or transverse myelopathy (most patients have some degree of weakness and spasticity of the legs). However, we have encountered two cases of asymmetric and profound atrophic weakness of the arms that began almost two decades after the shock and progressed over many years without long tract signs, both with a previously presumed diagnosis of amyotrophic lateral sclerosis. In contrast to injuries due to hightension current, which affects mainly the spinal white matter (see earlier), it is the gray matter that is injured in cases of spinal atrophic paralysis, at least as judged from the clinical effects. When the head is one of the contact points, the patient may become unconscious or suffer tinnitus, deafness, or headache for a short period following the injury. In a small number of surviving patients, after an asymptomatic interval of days to months, there has been an apoplectic onset of hemiplegia with or without aphasia or a striatal or brainstem syndrome, presumably due to thrombotic occlusion of cerebral vessels with infarction of tissue but this is not well studied. Lightning Injuries the factors involved in injuries from lightning are less well defined than those from electric currents, but the effects are much the same. The risk of being struck by lightning is about 30 times greater in rural areas than in cities.
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