Neuromuscular Complications of HIV Infections - Essay Example

NEUROMUSCULAR COMPLICATIONS OF HIV INFECTIONS HIV infection leads to a number of complications in the affected individuals. Patients may have more than one type of HIV-related neuromuscular complications. The type of the neuromuscular disorder depends upon the stage of the disease. A wide spectrum of neuromuscular complications is associated with the HIV infection, including the following: 1. Mononeuropathy multiplex 2. Acute or chronic inflammatory demyelinating polyradiculoneuropathy 3. Distal symmetric, painful and predominantly sensory neuropathy 4. Autonomic neuropathy 5. Anti-retroviral associated neuropathy 6. Polyradiculopathy 7. HIV myopathy 8. Zidovudine myopathy 9. HIV wasting syndrome 10. Neurotoxin associated peripheral neuropathy 11. Non-specefic myalgias occur as a part of the flu like illness during seroconversion. The relevant pathophysiological mechanisms may be: 1. Nutritional deficits (eg, vitamin B12) can be secondary to enteropathies and malabsorption caused by intestinal HIV, cytomegalovirus (CMV), or herpes simplex virus infection. 2. Drug toxicity: Zidovudine is associated with myopathy. Didanosine, dideoxycytidine, and stavudine can cause polyneuropathy, possibly in part due to mitochondrial toxicity. 3. Autoimmune mechanisms result in inflammatory demyelinating neuropathies, mononeuropathy multiplex, and polymyositis. 4. Co-infection with CMV, herpes simplex virus, varicella zoster virus, Mycobacterium avium-intracellulare, Treponema pallidum, and other bacteria can cause neuromuscular complications. 5. The likelihood of a particular syndrome correlates with viral load and CD4 lymphocyte counts. Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) and isolated acute cranial nerve palsies are common at seroconversion. Distal symmetric, often painful sensorimotor polyneuropathy and CMV infection are more common in the late stages of AIDS. 6. AIDP and CIDP may be the initial manifestation of disease, related to autoimmune dysfunction. CSF shows pleocytosis and increased protein. Nerve conduction studies (NCSs) and biopsy are compatible with demyelination. 7. Mononeuropathy multiplex is an inflammatory response in the early stages of disease. Late MM is typically associated with CMV infection. May appear as IDP or PP. EMG and NCS show axonal degeneration and asymmetric involvement. SDF shows pleocytosis and elevated protein level. 8. Progressive polyradiculopathy (PP) is typically associated with CMV and herpes infections. Highly active antiretroviral therapy (HAART) has reduced the incidence of PP. CSF shows pleocytosis and elevated protein level. It typically presents with a cauda equina–like picture, and EMG shows denervation of the lower extremities. NCSs are mildly slow. 9. Autonomic neuropathy usually presents with sexual dysfunction, diarrhea, and bladder dysfunction. It can be related to medication effects. 10. Myopathy shows proximal weakness and is confirmed with EMG. Elevated CK may also be seen, and muscle biopsy can be helpful, demonstrating necrosis and inflammation. HIV-related myopathy must be differentiated from toxin (AZT) related myopathies. (1) TABLE 8 Drugs Causing Neuropathies Axonal Vincristine (Oncovin, Vincosar PFS) Paclitaxel (Taxol) Nitrous oxide Colchicine (Probenecid, Col-Probenecid) Isoniazid (Laniazid) Hydralazine (Apresoline) Metronidazole (Flagyl) Pyridoxine (Nestrex, Beesix) Didanosine (Videx) Lithium Alfa interferon (Roferon-A, Intron A, Alferon N) Dapsone Phenytoin (Dilantin) Cimetidine (Tagamet) Disulfiram (Antabuse) Chloroquine (Aralen) Ethambutol (Myambutol) Amitriptyline (Elavil, Endep) Demyelinating Amiodarone (Cordarone) Chloroquine Suramin (Fourneau 309, Bayer 205, Germanin) Gold Neuronopathy Thalidomide (Synovir) Cisplatin (Platinol) Pyridoxine Adapted with permission from Masson C, Boulu P, Henin D. Les neuropathies iatrogenes. Rev Med Interne 1992;13(3):225-3 PERIPHERAL NEUROPATHIES OCCURING IN HIV INFECTION: Peripheral neuropathy is the commonest neurological disorder associated with HIV infection. Though symptomatic peripheral neuropathy is observed in 10% to 15% of HIV infected patients, pathologic evidence of involvement of peripheral nerve is seen almost all cases of end-stage AIDS patients. TYPES: The types of peripheral neuropathy include: 1. Distal sensory polyneuropathy 2. Inflammatory demyelinating polyradiculoneuropathy 3. Progressive polyradiculopathy 4. Mononeuritis multiplex 5. Autonomic neuropathy 6. Diffuse infiltrative lymphocytosis syndrome(DILS) associated neuropathy 1. DISTAL SENSORY POLYNEUROPATHY Etiology: Although the pathogenesis of distal sensory polyneuropathy is unclear, the condition is associated with deterioration of the patients immune system. A primary viral etiology is unlikely, since Human Immunodeficiency Virus does not infect peripheral nerve Schwann cells or axons. The similarities in clinical and pathologic findings of HIV-associated distal sensory polyneuropathy (DSP) and vitamin B12 deficiency-related peripheral neuropathy have led some investigators to propose vitamin B12 deficiency as a possible pathogenic mechanism in HIV-associated DSP. Mounting evidence suggests that cytokines (e.g., tumor necrosis factor-alpha, interleukin-1) may be involved in DSP by inhibiting nerve growth factor. Pathogenesis: DSP is characterized by the distal degeneration of long axons, the pattern often called as ‘dying back’, as the degeneration of the distal regions of the fibers is followed by the centripetal degeneration. Specifically the density of the unmyelinated fibers is reduced. Reduced intra epidermal nerve fiber density in the distal leg has been showed by the punch skin biopsies. This shows prominent involvement of the small, unmyelinated fibers. Dorsal root ganglion neuronal loss and selective degeneration of the gracile tracts characterized by loss of axons and myelin sheaths in the cervical and upper thoracic region has been described. This finding represents degeneration within the centrally directed extensions of the sensory neurons, and is the central nervous systems counterpart of the dying back process seen in the peripheral nerve. (2) Skin biopsy from a normal control (a) and a HIV patient with DSP (b). Note the decreased number of epidermal nerve fibers and formation of nerve fiber swellings (b) (bar, 50 µm). (2) Immunopathological studies have shown the macrophage activation with the local release of proinflammatory cytokines in the area of axonal degeneration. There has been consistent demonstration of increased frequency of Nageotte nodules. Nageotte nodules are compact areas of proliferation of satellite cells that frequently accompany dorsal root ganglion neuronal loss from any cause. (2) DRG inflammatory infiltrates are seen comprised mainly of lymphocytes and activated macrophages, with concomitant immunostaining for pro-inflammatory cytokines such as tumor necrosis factor (TNF)-, interferon- and interleukin-6. (2) Macrophage infiltration of peripheral nerve as observed by immunocytochemistry with anti-CD68 antibodies (a) Cross section. (b) Longitudinal section. (Bar, 50 µm.) (2) DRG pathology in HIV neuropathy is characterized by foci of macrophage-lymphocytic infiltration (a) and Nagoette nodules (b). Nagoette nodules are compact areas of proliferation of satellite cells that frequently accompany DRG neuronal loss from any cause. Infiltration by activated macrophages is demonstrated by immunostaining with anti-CD68 antibodies (c). (Bar, 50 µm.) (2) The main cause of the multifocal macrophage activation in the peripheral nerves is unknown. In one theory, it is postulated that a mild degree of distal axonal degeneration occurs because of nutritional deficiencies, alcohol exposure, substance abuse or other nonspecific factors. In the second theory, circulating activated monocytes and pro-inflammatory cytokines enter DRG and peripheral nerves in excessive numbers through a leaky blood-nerve barrier. This ingress of activated cells leads to further release of chemokines and cytokines with subsequent axonal and DRG neuronal injury. (2) Clinical features: Distal symmetrical polyneuropathy (DSP) may be clinically diagnosed in approximately 25%-30% of patients with AIDS. The incidence and prevalence of DSP increases with the progressive immunosuppression, that characterizes HIV-infection. It is important to differentiate DSP from other neuromuscular disorders associated with AIDS. Characteristic clinical symptoms of DSP include distal numbness, paresthesias and dysesthesias (painful, burning feet) generally beginning at the level of the toes and ascending to the feet, ankles and foreleg. In advanced cases distal and symmetrical involvement of the upper extremities and muscle weakness may be observed. The most important neurological signs are depressed or absent ankle reflexes relative to the knees, increased vibratory thresholds at the toes and ankles, reduced pain and temperature sensation in a stocking and glove distribution, and relatively normal joint position sensation. Hyperactive knee reflexes in the presence of DSP may indicate concurrent AIDS-associated CNS dysfunction, such as myelopathy. (3) Diagnostic procedures: The diagnosis of DSP can usually be established by an experienced clinician. Marra et al. have reported that a relatively simple screening and examination for neuropathy correlates with a neurologists diagnosis. The diagnostic approach to patients with DSP includes: (1) a comprehensive history to exclude other potential causes of neuropathy including diabetes mellitus, alcoholism, neurotoxin exposure, hereditary factors, and vitamin deficiency; (2) neurological examination; (3) electrophysiology and (4) appropriate blood studies. Electrophysiological studies (i.e. nerve conduction tests, electromyography) are usually not necessary for the clinical diagnosis of DSP in most patients, but may be helpful in complex cases. The main electrophysiologic abnormalities of DSP are: (a) reduction in sensory nerve conduction velocity and amplitude, particularly of the sural nerve; (b) prolonged late response latencies; (c) active or chronic partial denervation with reinnervation in distal leg muscles, on needle electromyography (EMG). These features are consistent with distal axonal sensory and motor polyneuropathy. (3) Management: The current treatment is primarily symptomatic. According to the ‘analgesic ladder’ as described by the World Health Organization, the patients with the mild pain, non-opioid analgesics such as acetaminophen and non-steroidal anti-inflammatory agents should be used. With the persistent and more disabling pain, tricyclic antidepressants or anticonvulsants may be useful. For a much higher level of pain, mild opioid combinations such as acetaminophen and codeine may be helpful. For severe pain, a potent opioid or a long lasting opioid agonist like methadone, morphine or fentanyl may be considered. (3) Differentiating HIV related DSP from nucleoside analogue related DSP: HIV related DSP develops over months and sometime even years. Nucleoside analogue related DSP develops after initiation of the therapy and usually takes weeks to develop. In case of nucleoside analogue related DSP, the disease usually improves after stopping the offending agent. It may take a few months. Some patients may go through a “coasting period” of four to eight weeks after drug withdrawal. In this period the symptoms worsens before improvement. (9) 2. INFLAMMATORY DEMYELINATING POLYNEUROPATHY: Pathogenesis: The exact pathology is still unknown. Evidence in favor of the autoimmune mechanism is the detection of anti-peripheral nerve myelin antibodies, at titers that parallel the course of illness. In advanced immunosuppression, it may directly affect the peripheral nerve. (3) Clinical features: It is clinically characterized by: (a) rapidly progressive muscle weakness involving two or more extremities, (b) generalized areflexia, (c) cranial nerve involvement (e.g. bilateral facial nerve paresis). The acute form (AIDP) often occurs at the time of HIV seroconversion. The chronic form (CIDP) has a slower onset and gradual progression. (3) Diagnostic procedures: Electrophysiological studies and CSF examination are helpful for diagnosis. They show conduction block, showing acquired demyelination and a lymphocyte pleocytosis along with an elevation of the CSF protein, respectively. (3) Treatment: Immunomodulation therapy such as corticosteroids, plasmapheresis and high dose I/V immunoglobulin are recommended. When the diagnostic studies show evidence of CMV infection, ganciclovir, foscarnet, or cidofovir, singly or in combination, is recommended. (3) 3. PROGRESSIVE POLYRADICULOPATHY: Etiology: Progressive polyradiculopathy (PP) occurs in patients with advanced immunodeficiency and is generally caused by the infection of the lumbosacral roots by the opportunist cytomegalovirus (CMV). Pathogenesis: Progressive polyradiculopathy usually occurs in patients with low CD4 cell counts. Clinical features: Progressive polyradiculopathy presents with paresthesias and radicular pain in the lower extremities involving the cauda equina distribution. This is followed by rapidly progressive flaccid paraparesis, lower extremity areflexia, and sphincter dysfunction often manifesting as urinary retention. In certain occasions a thoracic sensory level is present, suggesting concurrent myelopathy (3) Diagnostic procedures: The diagnosis of PP may be difficult, due to overlapping features of IDP, mononeuropathy multiplex and myelopathy. Electrophysiologic studies reveal widespread denervation in lower extremity and lumbar paraspinal muscles on needle EMG. CSF is characterized by the presence of marked polymorphonuclear pleocytosis, elevated protein, and hypoglycorrhachia. The diagnostic assay of choice is CSF PCR for CMV. Pathological studies indicate that HIV-related PP is usually a direct result of CMV infection. However, other causes such as neurosyphilis and lymphomatous meningitis may be responsible. (3) Management: With the advent of highly active antiretroviral therapy, the incidence of CMV-related PP has declined considerably. (3) 4. MONONEURITIS MULTIPLEX: Etiology: Mononeuritis multiplex actually is a group of disorders, not a true distinct disease entity. Typically, the condition is associated with (but not limited to) systemic disorders such as diabetes, vasculitis, amyloidosis, direct tumor involvement, polyarteritis nodosa, rheumatoid arthritis, systemic lupus erythematosus, and paraneoplastic syndromes. Mononeuritis multiplex also may be associated with Lyme disease, Wegeners granulomatosis, Sjögren syndrome, cryoglobulinemia, hypereosinophilia, temporal arteritis, scleroderma, sarcoidosis, leprosy, acute viral hepatitis A, and acquired immunodeficiency syndrome (AIDS). (4) Pathophysiology: Mononeuritis multiplex involves damage to at least 2 separate nerve areas. This condition can become progressively worse over time. The damage to the nerves involves destruction of the axon (ie, the part of the nerve cell that is analogous to the copper part of a wire), thus interfering with nerve conduction. Common causes of damage include a lack of oxygen from decreased blood flow or inflammation of blood vessels. Approximately 33% of cases originate from unidentifiable causes. (4) Clinical features: Patients with MM present with the acute onset of multifocal sensory or motor abnormalities in the distribution of cranial, mixed or cutaneous nerves. The form of mononeuropathy multiplex (MM) that occurs in relatively immunocompetent patients (CD4 lymphocyte counts greater than 200 cells/ml) is probably mediated by immune mechanisms. It is usually self-limited or has good response to immunosuppresive therapy, such as corticosteroids. A more extensive and progressive form of MM occurs when CD4 lymphocyte counts drop to low levels. Late stage MM may involve numerous nerves in two or more extremities or multiple cranial nerves. CMV is the most likely pathogen in the late form of MM. (3) Diagnostic procedures: The diagnostic algorithm for MM is similar for that in PP. Nerve conduction and EMG studies reveal multifocal and asymmetric pathology of cranial, sensory and motor nerves with axonal or demyelinating pathology. CSF analysis, including PCR assay for CMV, and sural nerve biopsy may reveal evidence of primary CMV infection of peripheral nerve. (3) Management: Management includes observation, particularly in early-onset MM, or immunomodulating therapy, including corticosteroids, plasmapheresis, or intravenous immunoglobulin (IVIg). Empirical therapy for CMV may be considered in late-onset MM, especially if there is evidence of CMV infection in CSF or nerve biopsy. (3) 5. AUTONOMIC NEUROPATHY: Clinical features: Several studies indicate that autonomic dysfunction, while often subclinical, is common in HIV infection, particularly in late stages of disease. Parasympathetic autonomic nervous system manifestations include resting tachycardia, impotence, and urinary dysfunction. Sympathetic autonomic nervous system dysfunction is characterized by orthostatic hypotension, syncope, diarrhea, and anhidrosis. (3) Pathogenesis: Multiple factors may be involved in the mechanism of autonomic dysfunction, including central and peripheral nervous system pathology, dehydration, malnutrition and drugs (e.g. vincristine, tricyclic antidepressants, and pentamidine). (3) Management: The primary treatment is supportive, including fluid management and control of cardiac arrythmias. (3) 6. DIFFUSE INFILTRATIVE LYMPHOCYTOSIS SYNDROME (DILS): Clinical features: Diffuse infiltrative lymphocytosis syndrome (DILS) is an unusual complication of HIV infection. It is characterized by CD8 hyperlymphocytosis that may involve peripheral nerve. DILS neuropathy may present as: symmetric or asymmetric sensorimotor neuropathy, distal sensory neuropathy, mononeuritis multiplex, or demyelinating polyneuropathy. (3) Pathogenesis: Host inflammatory responses to HIV infection are thought to account for peripheral nerve involvement in DILS (3) MYOPATHIES: The HIV related myopathies include: 1. HIV polymyositis 2. Zidovudine myopathy 3. Nemaline myopathy 4. Diffuse infiltrative lymphocytosis syndrome (DILS) 5. Inclusion body myositis 6. HIV wasting syndrome 7. Vasculitic processes 1. HIV POLYMYOSITIS: Idiopathic inflammatory myositis, known as polymyositis, is characterized by bilateral proximal muscle weakness (hip and shoulder girdle) and elevated serum CK levels. It can occur any time during the course of HIV infection; however, it usually occurs early. (11) The cause of polymyositis in HIV infection remains uncertain, but several theories have been proposed in the literature. One theory holds that it is related to direct invasion of the muscle by HIV, which causes a cytopathic effect and muscle necrosis. Supporting this proposal is the presence of HIV within skeletal muscle as determined by polymerase chain reaction. Another theory is that it is caused by an immunogenic response that elicits an inflammatory reaction within the muscle; involved muscle has been found to have a mononuclear cell infiltrate including CD4 and CD8 T lymphocytes. Finally, others propose that it is the result of an underlying opportunistic infection that causes a chronic antigenic stimulation leading to a reactive response in the affected muscle. (11) Diagnosis of polymyositis may be made using electromyography, MRI, or muscle biopsy. An electromyogram will reveal myopathic patterns of short duration, low amplitude, and polyphasic potentials with occasional fibrillation potentials at rest.[8] MRI studies will show a hyperintense signal on T2-weighted images without rim enhancement, but it may be difficult to discern anything on the T1-weighted images because of the isointense signal. Muscle biopsy demonstrates extensive perivascular and interstitial lymphocytic infiltrate and muscle necrosis.[8] While results of these studies commonly are abnormal in polymyositis, results of nerve conduction studies usually are normal, indicating a lack of neurologic injury. (11) The treatment options for polymyositis are somewhat limited. Discontinuation of any medication that may be associated with muscular irritation or inflammation should be considered. Treatment also generally involves an anti-inflammatory medication and, if necessary, use of a corticosteroid. (11) 2. ZIDOVUDINE MYOPATHY: Long-term zidovudine therapy can cause a dose-related mitochondrial toxicity that can precipitate myopathy. Studies indicate that as many as 17% of patients receiving long-term zidovudine therapy will experience some degree of zidovudine myopathy. Patients with zidovudine myopathy usually present with symptoms similar to those of polymyositis -- proximal muscle weakness, fatigue, and myalgia. Laboratory test results may also be similar, with elevated CK levels and electromyographic changes. (11) Discontinuation of zidovudine usually leads to regression of symptoms and normalization of laboratory and electromyographic findings. Although the myopathy is induced by zidovudine, it is probably multifactorial because zidovudine has not been shown to cause toxicity in muscle cell cultures or myopathy in noninfected persons. (11) In patients with myopathy who receive AZT therapy, withdrawal of AZT may result in clinical improvement. However, in our experience, AZT withdrawal led to increased muscle strength in only about 25% of patients, suggesting that HIV rather than AZT is the principal cause of myopathy in the majority of patients. Prednisone appears to be safe and effective in the treatment of HIV-associated myopathy. Small case series have reported clinical response to several other immunomodulating agents including plasmapheresis and intravenous immunoglobulin. (3) 3. NEMALINE MYOPATHY: Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a group of congenital, hereditary neuromuscular disorders that cause muscle weakness, generally nonprogressive, of varying severity. The term nemaline myopathy is derived from the Greek word ‘nema’ (7), which means thread like. Nemaline myopathy shows abnormal thread-like rods, called nemaline bodies, in the muscle cells. People with nemaline myopathy (or NM) usually experience delayed motor development and weakness in the arm, leg, trunk, throat, and face muscles. The disorder is often clinically categorized into several groups, including mild (typical), intermediate, severe, and adult-onset; however, these distinctions are somewhat ambiguous, as the categories frequently overlap. Respiratory problems are a primary concern for people with all forms of NM, and though in some severe cases they may threaten life expectancy, aggressive and proactive care allows most individuals to survive and lead active lives. (6) Despite the absence of muscle inflammation, positive responses to prednisone therapy have been observed, suggesting an autoimmune mechanism for the myopathy. 4. DIFFUSE INFILTRATIVE LYMPHOCYTOSIS SYNDROME (DILS): Diffuse infiltrative lymphocytosis syndrome (DILS) is characterized by a CD8+ lymphocytic infiltrate that occurs in association with human immunodeficiency virus (HIV) infection. This syndrome has been called HIV-associated salivary gland disease when it involves the salivary glands. Other tissues that may be infiltrated by CD8+ lymphocytes include the lacrimal glands and extraglandular tissues, such as kidney, muscle, nerve, liver, lung, gastrointestinal tract, and breast. The histologic picture found in the salivary glands resembles Sjögren syndrome, but distinctive immunologic, immunogenetic, and clinical differences exist. (10) Treatment of DILS combines antiretroviral therapy and steroids. Antiretroviral therapy may treat glandular swelling, sicca syndrome, and neuropathy. Corticosteroids are effective in treating life-threatening DILS manifestations, particularly lymphocytic interstitial pneumonitis or rapidly progressive neuromuscular complications. (9) 5. INCLUSION BODY MYOSITIS: A myopathy in every respect similar to inclusion-body myositis (IBM) is observed in rare patients infected by HIV-1 or HTLV-1 (human T-cell leukemia virus type 1).41 Muscle biopsy shows both PM-like endomysial inflammation with MHC-I/CD8 complex and degenerating features including fiber atrophy, red-rimmed vacuoles, amyloid deposits, and eosinophilic inclusions. Retroviral antigens have been detected only on endomysial macrophages but not within the muscle fibers, indicating that retroviruses do not directly infect the muscle but trigger an immune response identical to that occurring in sporadic IBM. (9) 6. HIV WASTING SYNDROME: A common problem among HIV-infected people is the HIV wasting syndrome, defined as unintended and progressive weight loss often accompanied by weakness, fever, nutritional deficiencies and diarrhea. The syndrome, also known as cachexia, can diminish the quality of life, exacerbate illness and increase the risk of death for people with HIV. (8) Wasting can occur as a result of HIV infection itself but also is commonly associated with HIV-related opportunistic infections and cancers. HIV wasting syndrome is diagnosed in HIV-infected people who have unintentionally lost more than 10 percent of their body weight. Most patients with advanced HIV disease and AIDS eventually experience some degree of wasting. (8) Many approaches have been used to reverse weight loss in HIV-infected people, including appetite stimulants, anabolic agents, cytokine inhibitors and hormones. Goals of therapy include both increase in body weight and increase in lean body mass (muscle). (8) A number of clinical trials of potential therapies for HIV wasting syndrome are ongoing or imminent in the NIAID-supported ACTG and Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). (8) CPCRA investigators are comparing the effectiveness of three nutritional regimens in increasing lean body mass and improving absorption of nutrients: whole protein and long-chain triglycerides plus a multivitamin; partially hydrolyzed protein and medium-chain triglycerides plus a multivitamin; a multivitamin alone. Another CPCRA trial compares: an oral anabolic agent, oxandrolone; an anabolic agent plus an appetite stimulant (megace); megace alone. As part of this study, some patients will take part in an exercise regimen. The investigators anticipate that this study will provide insights into the impact of increases in lean body mass and weight on survival and disease progression. In the ACTG, protocol 892 will attempt to correlate changes in viral load with changes in body composition and total body weight. ACTG 313 is comparing a regimen of megace and testosterone enenthate vs. megace alone. The primary objective of this study is to assess whether treatment with megace and testosterone leads to increased lean body mass, rather than the accrual of fat seen with megace alone. ACTG 329, a study enrolling women with HIV wasting syndrome, is assessing whether treatment with nandrolone results in weight gain and increases in lean body mass. Nandrolone is a male hormone called androgen with minimal masculinizing effects. (8) 7. VASCULITIC PROCESSES: Vascular inflammation appears to be multifactorial and may result from HIV-induced immunological abnormalities and exposure to a variety of xenoantigens such as HIV itself,60 other infectious agents, and drugs.Vasculitis may seldom present as a genuine acquired myopathy with proximal limb weakness, increased serum CK levels, and myopathic EMG.53 However, muscle necrotizing vasculitis is most often observed in patients with peripheral neuropathy.19 Vasculitic neuropathy usually presents as a distal symmetric polyneuropathy with weight loss, myalgias, weakness, and leg tenderness, and less often as asymmetric polyneuropathy or true mononeuropathy multiplex. (9) Treatment of HIV-related vasculitis is not clearly defined, but usually combines antiretroviral drugs and immunomodulatory agents, including intravenous immunoglobulins. Corticosteroids may be extremely effective. Cytotoxic agents commonly used in the treatment of arteritis are regarded as contraindicated in immunocompromised patients. So, by analogy with hepatitis B–related polyarteritis nodosa, a strategy combining antiviral treatments and plasma exchanges has been proposed. This strategy seems effective and does not jeopardize the outcome of AIDS, as could occur with cytotoxic agents. (9) CONCLUSIONS: While neuromuscular complications are not usually life threatening disorders in HIV-infected patients, they produce significant disabling symptoms in affected individuals. It is likely that in the current era of highly active antiretroviral therapy and prolonged life, the frequency of neurological disorders will increase. It is important that all clinicians caring for patients with HIV infection are familiar with the diagnosis and treatment of the associated neurological disorders. Currently available therapeutic agents, and those evolving from ongoing clinical trials, may provide significant improvement in the quality of life in these patients. (5) BIBLIOGRAPHY: 1. Florian P Thomas, MD, MA, PhD, DrMed. HIV Associated Neuromuscular Complications [online]. 2006 [cited 2007 Nov 30]. Available from: http://www.emedicine.com/neuro/topic457.htm 2. Sanjay C. Keswania, Carlos A. Pardoa, Catherine L. Cherry, Ahmet Hokea, Justin C. McArthura. HIV Associated Sensory Neuropathies [online]. 2002 [cited 2007 Nov 30]. Available from: http://www.medscape.com/viewarticle/445189_print 3. E. A. Wulff and D. M. Simpson. HIV-associated peripheral nervous system complications [online]. 1999 [cited 2007 Nov 30]. Available from: http://aidscience.org/neuroaids/articles/Neuro2(3).asp 4. Paul V Brooks, MD. Mononeuritis Multiplex [online]. 2006 [cited 2007 Nov 30]. Available from: http://www.emedicine.com/pmr/topic80.htm 5. E. A. Wulff and D. M. Simpson. HIV-associated Peripheral Nervous System Complications [online]. 1999 [cited 2007 Nov 30]. Available from: http://aidscience.org/neuroaids/zones/articles/1999/03/Complications/index.asp#Myopathy 6. Nemaline Myopathy [online]. 2007 [cited 2007 Nov 30]. Available from: http://en.wikipedia.org/wiki/Nemaline_myopathy 7. By Timothy J. Peters, Victor R. Preedy. Skeletal Muscle: Pathology, Diagnosis and Management of Disease [online]. 2002 [cited 2007 Nov 30]. Available from: http://books.google.com.pk/books?id=4dIszq3Qqv8C&pg=PA378&ots=lQVbqoi03i&dq=management+of+nemaline+myopathy&sig=aVw69LaqiOZ1qeARlRnk1lvhIo0 8. U.S National Institute of Allergy and Infectious Diseases. HIV Wasting Syndrome [online]. 1997 [cited 2007 Nov 30]. Available from: http://209.212.93.18/content/living/art6604.html 9. Francois-Jerome Authier MD, Patrick Chariot MD, PhD and Romain K. Gherardi, MD. Skeletal Muscle Involvement in Human Immunodeficiency Virus (HIV)-Infected Patients in the Era of Highly Active Antiretroviral Therapy (HAART). 2005 [cited 2007 Nov 30]. Available from: http://academia-research.com/files/instr/192900_myopathy%20in%20HIV.pdf 10. Carole P. McArthur, MD, PhD; Antonio Subtil-DeOliveira, MD; Dennis Palmer, DO; Russell M. Fiorella, MD, MBA; Steven Gustafson, DO; Daniel Tira, PhD; Roberto N. Miranda, MD. Characteristics of Salivary Diffuse Infiltrative Lymphocytosis Syndrome in West Africa [online]. 2000[cited 2007 Nov 30]. Available from: http://arpa.allenpress.com/arpaonline/?request=get-document&doi=10.1043%2F0003-9985(2000)124%3C1773:COSDIL%3E2.0.CO%3B2 11. The AIDS Reader [online]. 2003 [cited 2007 Nov 30]. Available from: http://www.medscape.com/viewarticle/450275_2 Read More