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Neurology 31: 730–735 315 Polyneuropathy and chemotherapy Toxic neuropathies caused by chemotherapy are usually dose-dependent discount ginette-35 2 mg amex, and have a potential reversibility after termination of the drug treatment ginette-35 2 mg cheap. Little is known about the influence of preexisting polyneuropathies in the development of a chemotherapeutically induced neuropathy (except vincristine given in patients with hereditary sensorimotor neuropathy) 2 mg ginette-35 fast delivery, and the toxicity of only a few drug combinations have been described generic 2 mg ginette-35 overnight delivery. This is of importance as chemo- therapy is not always used as a single agent therapy, but patients often receive drug combinations or second line therapy. Additionally also biological agents such as antibodies, interferons, cytokines and vaccines are used in cancer therapy and also have a risk of inducing polyneuropathies. Clinical distribution: Most neuropathies caused by chemotherapeutic agents are symmetric and length dependent, with a stocking glove distribution of sensory loss. Sensory symptoms and distal weakness ( lower extremities) occur. The development of distal sensory symptoms (numbness or paresthesias) can be used as a possible sign of neurotoxicity. Overview of the most frequently used chemotherapeutic agents causing poly- neuropathy Cisplatinum and • Cumulative dose approximately: Frequent derivatives 400 mg • Sensory neuro(neurono)pathy, with dysfunction of large fibers, ataxia • Persistence despite discontinuation (“coasting effect”). Combination Paclitaxel) involved with cisplatinum increases toxicity Vinca alkaloids Sensorimotor polyneuropathy, all fibers Frequent (vincristine and involved. Distal paresthesias (as initial derivatives) sign), areflexia, foot drop. Rarely: cranial nerves, or autonomic symptoms VM-26 and VP-16 Mild sensorimotor polyneuropathy Rare 316 Vinca alkaloids Genetic testing NCV/EMG Laboratory Imaging Biopsy + Symptoms Paresthesias on fingers and toes, sensory loss for pin prick and light touch. Clinical syndrome/ Dose dependent mixed sensorimotor polyneuropathy. Pathogenesis Vinca alkaloids bind to microtubules and interfere with their assembly. Structur- al changes account for abnormal axoplasmic transport and are related to axonal degeneration. Diagnosis Electrophysiology: axonal damage with an EMG that shows neurogenic changes. Differential diagnosis Paraneoplastic neuropathy, other chemotherapeutic agents. Prognosis Potentially reversible, sensory symptoms improve within some months. Rapid onset, often with burning pain, with rare weakness. While cisplatin and carboplatin have a similar spectrum of dose dependent Clinical syndrome/ neuropathy, oxaliplatin has two types of toxicity. Patients experience dysesthesias and paresthesias, aggravated by cold. The symptoms recur after each chemotherapy cycle with oxaliplatin. Additional symptoms also include eye and jaw pain, leg cramps, and voice changes. The chronic toxicity is a dose dependent polyneuropathy, resembling cis platinum neuropathy. Proximal and distal weakness and sensory loss, ataxia. Random demyelination may interfere with microtubular transport. Electrophysiology: axon loss changes with small sensory and motor evoked Diagnosis responses, denervation on EMG Drug withdrawal. Symptoms may increase after cessation of therapy (“coast- Therapy ing“).

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He also has evidence of acne generic ginette-35 2 mg amex, and there is a tan 2mg ginette-35 free shipping, oval macule measuring 3 cm on his chest safe 2 mg ginette-35. You believe he may have neurofibromatosis-1 (NF-1 cheap 2mg ginette-35, also known as von Recklinghausen disease). Which of the following statements about neurofibromatosis is false? There are two major forms, NF-1 and neurofibromatosis-2 (NF-2) B. Both NF-1 and NF-2 are inherited in an autosomal recessive pattern C. NF-1 is characterized by neurofibromas, café au lait spots, iris hamar- tomas (Lisch nodules), neurologic impairment, and bone abnormalities D. NF-2 is less common and is characterized by bilateral acoustic neuro- mas; skin findings are less common than in NF-1 Key Concept/Objective: To understand the key features of the two major forms of neurofibro- matosis and their pattern of inheritance It is most likely that this patient has NF-1 (von Recklinghausen disease) and that he inher- ited it from his father. Neurofibromas typically appear at puberty and are progressive, as are the other manifestations of neurofibromatosis. Such manifestations include café au lait spots; Lisch nodules; involvement of the spine and peripheral nerves with tumors; neuro- logic impairment; bony abnormalities; and a predisposition to malignancy. NF-2 is char- acterized by bilateral acoustic neuromas; NF-2 usually presents as hearing loss in the sec- ond or third decade of life. This form of neurofibromatosis is less common than NF-1 and is less likely to present with skin findings. Other features of NF-2 include meningiomas, gliomas, and cataracts. Both of these forms of neurofibromatosis are inherited in an auto- somal dominant fashion, with near complete penetrance. A 17-year-old African-American adolescent presents with swelling of her earlobes; she had them pierced a few months ago. She can no longer put her earrings on and is distraught about her appearance. Examination is remarkable for hyperpigmented, shiny, smooth tumors measuring 1 to 2 cm that are located around the areas of her ear piercing. There are small, crablike extensions from the lesions. You believe the patient has developed keloids at the sites of her ear piercing. They are more common in African Americans, Hispanics, and those with a family history of keloids B. Risk factors for the development of keloids include wound tension, ear piercing, healing by second intention, young age, and deep laceration Key Concept/Objective: To understand the presentation of keloids, to know those who are at greatest risk for developing them, and to be aware of some of the common methods of treatment Keloids represent an abnormal response to tissue injury, manifested as delayed, excessive proliferation of scar tissue. They do not regress and often cause pain, burning, and pruri- tus. They are more common in African Americans, Hispanics, and those with a family his- tory of keloids. Risk factors for their development include wound tension, ear piercing, healing by second intention, young age, and deep laceration. Intralesional steroids admin- istered at doses of 10 to 40 mg/ml every month for up to 6 months have been shown to effectively flatten keloids, although several side effects may occur. Cryotherapy given as a 30-second application once a month for 3 months has been found to be a safe and effec- tive treatment. A 16-year-old female patient comes to your office complaining of acne, which she has had for 3 years. The lesions have been small in size, not painful, and not swollen, and they have not progressed over this period. She says the acne is bothering her, and she would like to be treated. On physical examination, the patient is found to have multiple comedones measuring 0. Which of the following is the most appropriate treatment for this patient?

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BCG sepsis is the most serious complication and can be life-threatening cheap ginette-35 2mg with amex. Systemic involvement is treated with triple-antibiotic antituberculous therapy for 6 months order ginette-35 2 mg without prescription. A 30-year-old woman comes to your clinic complaining of right-side flank pain and macroscopic hema- turia 2 mg ginette-35 visa. You make a presumptive diagnosis of nephrolithiasis and order a CT scan safe 2 mg ginette-35, which shows no stones; however, the report describes three masses in the right kidney, the largest measuring 5 × 4 cm; two mass- es are seen in the left kidney, the larger measuring 3 × 3 cm. You call your patient to discuss these CT findings, and you ask her about her family history. She says her sis- ter had a brain tumor that caused her to have gait problems, and a brother had kidney cancer. Polycystic kidney disease with malignant transformation D. Von Hippel-Lindau (VHL) disease Key Concept/Objective: To know the manifestations of VHL disease Most renal cell carcinomas occur sporadically, but about 4% of cases present in an inher- ited pattern. Such familial cancers include VHL disease and familial papillary renal cell cancers. Compared with sporadic cases, renal cell cancer in the VHL syndrome tends to be multifocal and bilateral and to appear at a younger age. Polycystic kidney disease is not a risk factor for renal cell cancer. However, a threefold- to sixfold-higher incidence of renal cell cancer has been found in the chronic dialysis population as well as in renal trans- plant recipients, presumably because of the development of acquired cystic kidney disease. A 25-year-old man comes to the clinic after finding a painless mass on his right testicle. He has no symp- toms except for mild pain on the right flank and headache of new onset. The physical examination shows a 2 × 2 cm solid, hard mass on the right testicle. Physical examination shows no lymphadenopa- thy or other abnormalities. An ultrasound is obtained, which shows a mass on the right testicle consis- tent with a tumor. A chest x-ray shows multiple “cannonball” lesions in both lungs. A pelvic CT scan shows diffuse retroperitoneal lymphadenopathy. A magnetic resonance imaging scan of the brain also shows multiple masses consistent with metastatic disease. On the basis of these findings and the overall prognosis, how would you approach this patient? Refer to surgical oncology and radiation oncology for orchiectomy and radiotherapy B. Explain the bad prognosis of his extensive disease and refer to pallia- tive care C. Refer to surgical oncology and radiation oncology for orchiectomy with radical retroperitoneal lymph node dissection and radiotherapy Key Concept/Objective: To outline the management of metastatic testicular cancer For testicular cancer patients with lymph node metastases measuring more than 5 cm in diameter and for those with visceral metastases (e. The early combination of cisplatin, vinblastine, and bleomycin (the PVB regimen) produced cures in up to 70% of cases. Subsequently, a less toxic regimen, in which vinblastine was replaced by etoposide, was tested and shown to be equivalent to the PVB regimen. Metastatic diseases in the brain and liver, and possibly in bone, are associated with a worse prognosis. However, it must be emphasized that cure is possible in patients in the worst prognostic groups; even patients with brain metastases may be cured by aggressive multimodality treatment. Orchiectomy, radiotherapy, and rad- ical retroperitoneal lymph node dissection are used in early stages of testicular cancer, when the disease is confined to the testicles or when the lymph node metastases are small- er than 5 cm. A 32-year-old man with a recently diagnosed metastatic seminoma is started on a regimen of cisplatin, vinblastin, and bleomycin. His initial human chorionic gonadotropin (hCG) level is 80 mIU/ml.

Vestibular maneuvers buy ginette-35 2mg low price, including Nylen-Barany generic ginette-35 2mg with amex, are often positive cheap ginette-35 2 mg free shipping, reproducing the patient’s complaint cheap 2mg ginette-35 visa. Because the symptoms and findings of Ménière’s disease and acoustic neuroma are so similar, MRI is helpful to exclude tumor. A number of other studies are typically performed by specialists, including auditory evoked potentials. Medications A variety of medications can potentially affect hearing acuity. However, the most com- mon are as follows: antibiotics (aminoglycosides); quinine derivatives; antineoplastics (platinum-based and methotrexate); loop diuretics; and nonsteroidal antiinflammatories, both salicylate-based and others. When hearing loss is identified, obtain a list of all agents taken by the patient and determine whether any have a potential ototoxicity. Medication- related ototoxicity can be permanent or reversible, depending on the agent. Ringing (Tinnitus) Ringing in the ears (tinnitus) is most often related to the use of ototoxic drugs. It is also associated with continued exposure to loud noise and environmental chemical exposure. Tinnitus refers to a wide range of sounds mimicking whistles, crickets, ringing, buzzing, and the like. Tinnitus is associated with many of the causes of hearing loss. History Specific history should include current medications, the amount and frequency of dosing, and recent exposure to loud noise or chemical agents through activities including work, hobbies, or recreation. A history of other ear disorders and symptoms should be obtained, including labyrinthitis, Ménière’s disease, or progressive hearing loss. Physical Examination A thorough ENT and neurological examination should be performed. Unless some abnor- mality of structure or infection is expected, the physical examination should be normal. There may be a decrease in gross hearing acuity and in performance during a tuning fork exam, as tinnitus is associated with the causes of hearing loss. Ear, Nose, Mouth, and Throat 95 Box 5-1 Common Causes ofTinnitus Ménie`re’s disease Acoustic trauma Neoplasms Cerumen or foreign body Infections Ototoxic medications Diagnostic Studies Diagnostic studies are related to the specific suspected etiology associated with the tinnitus but should include audiometry. Ear Fullness The etiology of ear fullness is multidimensional. Fullness can be related to fluid in the mid- dle ear as a result of otitis media or changes in barometric pressure. The most common causes vary by age; children are more likely to experience ear fullness associated with OME, whereas older adults are more likely to have cerumen impaction. History Check for seven dimensions of the symptoms, and especially note the timing of the symp- tom. Determine whether the fullness is affected by the patient’s position. Identify any concurrent or recent other ENT symptoms or respiratory conditions. Physical Examination Examine the external ear structures. Manipulate the external ear to identify any tenderness before inserting the otoscope speculum. Observe the TM to detect any dullness, decreased light reflex, bulging, retraction, or inflammation, which may indicate fluid or infection. Diagnostic Studies Pneumatic otoscopy will assist in determining the presence of fluid in the middle ear.

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