HIV/AIDS Related Myeleterosis and Peripheral Neuropathy

  • Hongjun Li
Chapter

Abstract

Up to now, reports about HIV/AIDS related myelopathy remain rare in China. McArthur collected 186 cases of HIV/AIDS complicated by brain and peripheral nerve lesions in the year of 1987 [11]. Only 13 cases had HIV/AIDS related myelopathy, accounting for 7 %. Levy et al. [8] reported the occurrence of HIV/AIDS related myelopathy is 2–22 % based on literature analysis. In another group of 150 patients with AIDS, 42 had HIV/AIDS related myelopathy, in which 24 % with spinal degeneration, 38 % with viral infection, 5 % with toxoplasmosis, 2 % with myelitis and the other 31 % with no pathological diagnosis [2]. Surprisingly, myelopathy is commonly found by autopsy. Peter and his fellow researchers [14] found 50 % of the total 178 patients with AIDS have myelopathy, with 29 % spinal degeneration, 5 % HIV myelitis, 8 % viral infection, 7 % other infections and 2 % lymphoma. Budka [3] retrospectively reviewed autopsies of 475 death cases from AIDS in 1997 and found that 22.5 % had spinal degeneration, 6 % myelitis, 58 % viral infection and 4.1 % fungal, bacterial and protozoal infections as well as 2.3 % lymphoma. Since the year of 1997, knowledge about the clinical treatment for HIV/AIDS complicated by myelopathy has been greatly improved.

Keywords

Spinal Cord Varicella Zoster Virus Epidural Abscess Toxoplasma Infection Abscess Wall 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

14.1 Introduction of HIV/AIDS Related Myelopathy and Peripheral Neuropathy

Up to now, reports about HIV/AIDS related myelopathy remain rare in China. McArthur collected 186 cases of HIV/AIDS complicated by brain and peripheral nerve lesions in the year of 1987 [11]. Only 13 cases had HIV/AIDS related myelopathy, accounting for 7 %. Levy et al. [8] reported the occurrence of HIV/AIDS related myelopathy is 2–22 % based on literature analysis. In another group of 150 patients with AIDS, 42 had HIV/AIDS related myelopathy, in which 24 % with spinal degeneration, 38 % with viral infection, 5 % with toxoplasmosis, 2 % with myelitis and the other 31 % with no pathological diagnosis [2]. Surprisingly, myelopathy is commonly found by autopsy. Peter and his fellow researchers [14] found 50 % of the total 178 patients with AIDS have myelopathy, with 29 % spinal degeneration, 5 % HIV myelitis, 8 % viral infection, 7 % other infections and 2 % lymphoma. Budka [3] retrospectively reviewed autopsies of 475 death cases from AIDS in 1997 and found that 22.5 % had spinal degeneration, 6 % myelitis, 58 % viral infection and 4.1 % fungal, bacterial and protozoal infections as well as 2.3 % lymphoma. Since the year of 1997, knowledge about the clinical treatment for HIV/AIDS complicated by myelopathy has been greatly improved.

HIV/AIDS related myelopathy had been rarely reported probably due to the difficulty in its differential diagnosis from encephalopathy based on the clinical manifestations and the difficulty in its diagnosis resulted from its complex lesions.

HIV infected patients commonly have complicated peripheral neuropathy, which is clinically manifested as neuropathic pain. Its incidence rate is much higher than myelopathy and the diagnosis rarely depends on the diagnostic imaging. In cases complicated by central nervous disorders, the clinical manifestations are complex. The diagnosis of cerebral and spinal lesions can be greatly facilitated by the diagnostic imaging.

In the year of 1985, Petito et al. [15] confirmed by pathological examinations that HIV/AIDS related spinal lesions are commonly accompanied by spinal degeneration, peripheral neuropathy and dementia and about 20 % have ataxia and sphincter impairments. Nevertheless, there still have no explicit diagnostic criteria. Due to the high degree of immunodeficiency in patients with AIDS, spinal lesions are commonly secondary rather than primary. Abnormal findings of myelopathy by the diagnostic imaging are usually demonstrated in the advanced stage of AIDS. The commonly seen HIV/AIDS complicated by myelopathy include viral myelitis, spinal bacterial infection and myeloma.

14.1.1 HIV/AIDS Related Spinal Toxoplasma Infection

Patients with AIDS are highly susceptible to toxoplasma infection, especially recurrence of latent infection. In such cases with acquired toxoplasmosis, lymphadenopathy may be less evident but acute fetal infections with extensive dissemination may occur. The clinical manifestations include high fever, pneumonia, skin rash, hepatosplenomegaly and myocarditis. Sometimes, spinal toxoplasmosis occurs as a complication of HIV/AIDS.

14.1.2 HIV/AIDS Related Viral Myelitis

Patients with AIDS can develop myelitic lesions induced by multiple viruses, such as cytomegalovirus (CMV), varicella zoster virus (VZV) and herpes simplex virus (HSV). It is commonly believed that the lesion is resulted from demyelination secondary to infection and is related to the autoimmunity. The foci can be found at any part of spinal white matter, with characteristic demonstrations of concurrent lesions around the veins and under the soft pia mater in the diseased white matter area. The lesion may involve the gray matter, with a diffusive distribution.

Viral myelitis has an acute onset, with initial clinical manifestations of fever, headache, nausea and vomiting 1–2 weeks prior to the onset. The following manifestations are anxiety, deliration, lethargy, stiffness and coma. The imaging demonstrations are not characteristic, making it difficult to be differentiated from acute multiple sclerosis. CT scanning demonstrates diffusive low-density area in the spinal white matter. MR imaging demonstrates swollen spinal cord, with equal or low signal of T1WI and high signal of T2WI. The focus is prone to be complicated by hemorrhage and swollen and enlarged spinal cords show no enhancement by enhanced imaging. In the chronic stage, the spinal cord may be shrunk and thin, with dilated central duct. However, the manifestations are not specific, making it difficult to be differentiated from lymphoma.

14.1.3 HIV/AIDS Related Spinal Bacterial Infection

HIV/AIDS complicated by spinal tuberculosis [4] and syphilis [12] have been reported. Tuberculosis mycobacterium can cause meningoradiculitis or intramedullary tuberculoma. Syphilis may cause syphiloma within the spinal canal. In patients with frequent intravenous drug abusers, bacteremia commonly occurs, with possible occurrence of epidural abscess that may extend to paravertebral. The most common pathogen of epidural abscess is staphylococcus; tuberculosis mycobacterium, Nocardia and Aspergillus [13] are also reported to cause high fever with progression to paralysis within 24–72 h. The lesion may be sub-acute, with nerve symptoms in 1 week or several months. Intramedullary infection is resulted from venous occlusion by bacteria colonies, leading to spinal venous occlusion. CT and MRI scanning can definitively demonstrate the location and range of the abscesses. Plain CT scanning demonstrates local spinal thickening, irregular morphology, and clearly defined boundary of intraspinal foci. The enhanced scanning shows ring shaped enhancement of the capsule. MRI demonstrates low signal of T1WI and T2WI of the capsule, low signal of T1WI and high signal of T2WI of the abscess fluid. The enhanced MR imaging demonstrates ring shaped enhancement of abscess wall by T1WI. Both CT and MRI demonstrate flaky or nodular enhancement before the formation of large abscess cavity at the inflammation phase.

14.1.4 HIV/AIDS Related Myeloma

Due to dependence on the immune response, patients with AIDS rarely have myeloma. The rarely found reports also include cases of spinal lymphoma and plasmocytoma. Lytic enzyme in the extraspinal Kaposi’s tumor (KS) can also impair the spinal cord. In HIV/AIDS related neoplasms, the accompanying spinal metastasis tumor may occur.

14.1.5 Other HIV/AIDS Related Diseases

HIV/AIDS related multiple sclerosis is related to HIV-induced immunodeficiency, with acute or sub-acute onset. Its initial symptoms include bilateral or unilateral visual impairment. Spinal cord lesions commonly occur in the dorsal horn, with clinical manifestations of limbs pain, paresthesia, weakness and paralysis of limbs or hemiplegia. Some patients may develop sensory disturbance, specifically sensing the plane as incomplete. Plain CT scanning demonstrations are negative; uneven ring shaped enhancement of the spinal cord in the acute phase can be found by enhanced scanning, with low sensitivity. Sagittal MR imaging demonstrates clearly the range of the lesions by T1WI and T2WI. In the acute phase, T1WI only demonstrates thickened spinal cord, with normal intraspinal signal; T2WI demonstrates intraspinal singular or multiple high signal foci, with space occupying effects of different degrees. By enhanced imaging, some foci are in ring shaped enhancement. Increased dosage of the contrast reagent can increase the detection rate of the foci.

Diagnostic examinations for HIV/AIDS related myelopathy include: For patients with spastic paralysis or paraplegia of the lower extremities, CSF test should be firstly performed to find the common pathogenic microorganisms and PCR can be performed to detect myelitis related viruses. For patients with large epidural abscess, lumbar puncture is of tremendous risk. CT scanning can effectively detect epidural lesions, but with poor demonstration of intraspinal lesions. MR imaging is ideal for clinical diagnosis of HIV/AIDS related myelopathy to distinguish epidural and subdural structures, demonstrate spinal degeneration, extensive necrosis and hemorrhage. When MR imaging is not available or feasible, enhanced CT scanning can facilitate the preliminary diagnosis.

14.2 HIV/AIDS Related Spinal Toxoplasma Infection

14.2.1 Pathogen and Pathogenesis

Toxoplasma invades the human body via the digestive tract. Firstly, sporozoites or trophozoites invade intestinal mucosal cells and reproduce there to cause the rupture of the intestinal mucosal cells. The released trophozoites are disseminated along with blood or lymph flow throughout the body to cause parasitemia. The further involvement of the spinal tissues renders toxoplasma rapidly divide and proliferate in tissue cells to cause damages to the host cells and invasion of their adjacent cells. The repeated pathogenic processes cause necrosis of local tissue cells to form necrotic foci and to induce acute inflammatory responses predominantly with monocytes infiltration.

14.2.2 Pathophysiological Basis

By autopsy, the spinal cord is found to have tissue liquification and necrosis, with few inflammatory cells infiltration. Within the necrotic foci, there are cystic toxoplasma trophozoites, as granules of different sizes.

14.2.3 Clinical Symptoms and Signs

Typical spinal toxoplasmosis has a sub-acute onset, with clinical manifestations of headache, hemiplegia, seizure, visual disturbance, unconsciousness and even coma. The symptoms of fever and meningeal irritation are rarely found.

14.2.4 Examinations and the Selection of Examinations

14.2.4.1 Examinations for Pathogens

Cerebrospinal fluid, sputum, pleural effusion, ascites and marrow are collected for smears. Alternatively, lymphnodeimprintslide and tissue sections may also be prepared. Subsequently routine staining or immunocytochemistry can be performed to detect toxoplasm trophozoites or cysts. Moreover, the toxoplasm can be isolated by inoculating the above specimens in mice or by tissue culture. In recent years, nucleic acid hybridization in situ or PCR has been used to examine toxoplasma DNA, which might facilitate diagnosis of toxoplasma infection. Especially, PCR examination of toxoplasma DNA in cerebrospinal fluid and amniotic fluid is of great significance for diagnosis of spinal toxoplasmosis and congenital spinal toxoplasmosis.

14.2.4.2 Immunological Assays

A widely used technology in recent years is to examine toxoplasma circulating antigen (CAg) in the serum or body fluid with specific antibody to toxoplasma. Toxoplasma CAg positive is an indicator of pathogen, facilitating the diagnosis of acute toxoplasma infection.

14.2.4.3 CSF Test

Cerebrospinal fluid (CSF) pressure is commonly normal, with yellowish appearance, positive globulin test and a slight increase in cell count, which is commonly (100–300) × 106/L and monocytes. The glucose level remains normal or decreased, with increased level of protein and normal level of chloride.

14.2.4.4 Diagnostic Imaging

MR imaging can clearly define the size, shape, location of the foci as well as their relationship with the adjacent tissues, which is of great importance to the diagnosis of cerebral toxoplasmosis and its outcomes.

14.2.5 Imaging Demonstrations

14.2.5.1 CT Scanning

The brain and spinal cord commonly have multiple foci. The plain CT scanning demonstrates thickened spinal cord, foci in equal or low signal, foci complicated by calcification in high signal, surrounding edema in strip liked low density foci, and ring liked and target shaped enhancement of foci by enhanced scanning.

14.2.5.2 MR Imaging

Plain MR imaging demonstrates thickened and swollen spinal cord, foci in short T1 and T2 signals, surrounding edema in long strip liked high T1 and T2 signals. By enhanced imaging, the foci are in ring shaped or target liked enhancement, highly indicative of spinal cord infection.

Case Study 1

A patient aged 36 years was confirmatively diagnosed as having AIDS by CDC, with positive toxoplasma IgG and a CD4 T cell count of 45/μl.
Fig. 14.1

(aj) HIV/AIDS related spinal toxoplasma infection. (ag) Pre-treatment. (h, j) Post-treatment. (a, b) Sagittal T1WI demonstrates round liked and slightly short T1 signal at C3–C4 level, equal T1 signal within it, swollen and thickened cervical spinal cord in the focal site. (c, d) Sagittal T2WI demonstrates long T2 signal of the focal margin with central even and short T2 signals, surrounded by spindle shaped edema. (e, f) Coronal and sagittal enhanced T1WI demonstrate obvious ring shaped enhancement of the foci. (g) Coronal enhanced T1WI demonstrates evident homogeneous enhancement of the foci. (h) Sagittal T1WI demonstrates shrunk foci. (i) Sagittal T2WI demonstrates ring shaped high signal of the foci with unobvious peripheral edema. (j) Saggital enhanced T1WI demonstrates shrunk foci with ring shaped enhancement

Case Study 2

A male patient aged 51 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 45/μl.
Fig. 14.2

(ad) HIV/AIDS related cerebral and spinal toxoplasma infection. (a) Coronal enhanced T1WI demonstrates ring shaped enhancement of the foci adjacent to the right ventricle, with slightly compressed and deformed right ventricle. (b) Sagittal enhanced T1WI demonstrates ring shaped enhancement of the foci posterior to the body of lateral ventricle. (c, d) Sagittal enhanced T1WI demonstrates irregular foci at C3–C4 level, with homogeneous enhancement and blurry borderline

Case Study 3

The male patient aged 41 years was confirmatively diagnosed as having AIDS by CDC. His CT4 T count was 55/μl.
Fig. 14.3

(ag) HIV/AIDS related spinal toxoplasma infection. (a, b) Sagittal T2WI demonstrates slightly swollen and enlarged cervical spinal cord, irregular short T2 signal of the foci at C3 level and peripheral long strips of edema with long T2 signal. (c) Sagittal enhanced T1WI demonstrates annular ring shaped enhancement of the spinal foci. (d) Coronal enhanced T1WI demonstrates inhomogeneous enhancement of the focuses. (e, f) Sagittal T2WI demonstrates no foci after treatment. (g) Coronal T1WI demonstrates no detectable foci

14.2.6 Criteria for the Diagnosis

The definitive diagnosis is based on the corresponding clinical manifestations. CSF test demonstrates a slight increase of white cells, increased proteins and positive serum toxoplasma antibodies IgA and IgG. The diagnosis can also be made based on biopsy of cerebrospinal fluid and histopathological examination.

14.2.7 Differential Diagnosis

14.2.7.1 Viral Myelitis

Viral myelitis has typical manifestations of concurrence of lesions around the veins and under the soft pia mater in the diseased white matter, with possible involvement of the gray matter, in a diffusive distribution. The disease has an acute onset, with initial clinical symptoms of fever, headache and nausea and the following symptoms of irritation, delirium, sleepiness and coma. The imaging demonstrations are not characteristic. CT scanning demonstrates diffusive low density areas in the white matter of the spinal cord. MR imaging demonstrates swollen spinal cord, equal or low signal by T1WI and high signal by T2WI. The foci are susceptible to bleeding. Enhanced scanning demonstrates no enhancement of the foci. The differential diagnosis depends on the test for serum anti-toxoplasma antibody, CSF biopsy and histopathological examination.

14.2.7.2 Spinal Bacterial Infection

Plain CT scanning demonstrates locally thickened spinal cord with irregular morphology, clearly defined border of intraspinal foci, and ring shaped enhancement of envelope membrane by enhanced scanning. Plain MR imaging demonstrates long T1 and short T2 signals of the envelope membrane, long T1 and T2 signals of the inner abscess fluids; and ring shaped enhancement of the abscess wall by enhanced imaging. CT and MRI demonstrate flaky or nodular enhancement before the formation of larger abscess cavity in the inflammation phase. By the diagnostic imaging, it is difficult to differentiate spinal bacterial infection from spinal toxoplasma infection. Laboratory tests and histopathological examinations should be performed for their differential diagnosis.

14.3 HIV/AIDS Related Viral Myelitis

14.3.1 HIV/AIDS Related Herpes Simplex Virus Myelitis

14.3.1.1 Pathogen and Pathogenesis

Herpes simplex virus (HSV) consists of double-stranded DNA genome and is transmitted via intimate or sexual contacts to patients and healthy virus carriers or via droplets. Virus in latency can be activated in immunocompromised AIDS patients to cause more severe symptoms and organ damages. HSV latent in the neural ganglia is activated when cellular immunodeficiency occurs, followed by its descending course along the sensory nerve fiber axon to its terminal to infect the neighboring skin or mucosa epithelium and to proliferate there. Therefore, recurrent local herpes is caused. This is known as the neuron triggering theory.

14.3.1.2 Pathophysiological Basis

The pathological changes include inflammation and degeneration, with manifestations of edema and degeneration of soft pia mater and spinal cord, infiltration and effusion of monocytes and lymphocytes, swollen neural cells and detectable intranuclear inclusions in the infected cells. The infected cells commonly fuse into multinuclear giant cells. In severely ill patients, myelomalacia, spinal necrosis and hemorrhage, nerve cells atrophy in the chronic phase, loss of myelin, axon degeneration and gliocyte hyperplasia may occur.

14.3.1.3 Clinical Symptoms and Signs

For patients of the initial occurrence, due to no produced antibody in the acute phase, they usually show symptoms of fever or irritation, general symptoms of local lymphadenectasis, muscular pain, and disseminative infections. The spinal cord is often invaded, including transverse injury, with initial symptoms of lower extremities weakness, sensory disturbance and urine retention. Brown-Sequard syndrome has manifestations of unilateral extremities weakness, diminished deep sensation and involved contralateral algesia and thermesthesia.

14.3.1.4 Examinations and Their Selection

Laboratory Test

HSV-DNA-PCR antibody in the CSF and serum specific IgM is one of the laboratory tests for accurate and rapid diagnosis.

Diagnostic Imaging

CT scanning has a limited diagnostic value. MRI can clearly define the size, shape, location of the foci as well as their relationship with the surrounding tissues, facilitating the clinical diagnosis.

14.3.1.5 Imaging Demonstrations

CT Demonstrations

CT scanning usually is applied together with myelography, with demonstrations of slightly thickened spinal cord with uneven density.

MRI Demonstrations

MRI provides evidence for understanding of HSV myelitis, whose demonstrations include one or several thickened spinal segments with irregular long T1 and T2 signals, bleeding foci, swollen and thickened spinal cord and no enhancement by enhanced imaging. In the chronic phase, the demonstrations are shrunk and thinner spinal cord, accompanying enlargement of the central canal, but no MRI demonstrations characteristic of HSV myelitis.

Case Study

A male patient aged 38 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 55/μl.
Fig. 14.4

(ac) HIV/AIDS related herpes simplex virus myelitis. (ac) Sagittal T1WI demonstrates strip liked short T1 signals at C2–C5 level and slightly swollen and enlarged cervical spinal cord at the lesion

14.3.1.6 Criteria for Diagnosis

  1. 1.

    Typical clinical manifestations of limbs dysfunction as well as urinary and fecal incontinence.

     
  2. 2.

    Increased CSF proteins

     
  3. 3.

    Swollen spinal cord by MR imaging, with equal T1 and long T2 signals.

     

14.3.1.7 Differential Diagnosis

HIV/AIDS related multiple scleroses are related with HIV-induced immunodeficiency, with an acute or sub-acute onset. Its initial symptoms include bilateral or unilateral visual disturbance. Plain CT scanning demonstrations are commonly negative, but demonstrations of uneven ring shaped enhancement of spinal cord in the acute phase by enhanced scanning, with a low sensitivity. Sagittal MRI of T1WI and T2WI clearly demonstrate the range of the lesions. By T1WI, the demonstration of the acute phase includes thickened spinal cord, with normal signal within the spinal cord. T2WI suggests singular or multiple high signal foci, with accompanying space occupying effects of various degrees. By enhanced imaging, some foci are demonstrated in ring shaped enhancement. Appropriate increase of the contrast reagent dosage can improve the detection rate of the foci. Acute multiple sclerosis has similar manifestations to the disease and their differential diagnosis should incorporate clinical and other examinations.

14.3.2 HIV/AIDS Related Cytomegalovirus Myelitis

14.3.2.1 Pathogen and Pathogenesis

Cytomegalovirus (CMV) infection is the most common viral opportunistic infection in AIDS patients, with an occurrence of 40 % in terminal patients with AIDS. By autopsy, the occurrence of HIV/AIDS related cytomegalovirus infection is up to 62 %. CMV can remain latent within the human body over a long period, reactivated and triggering onset of CMV infection due to compromised or deficient immunity. The virus can spread to impair other organs via viremia or carried by lymphocytes and monocytes. As a typically active infection, over 90 % patients are CMV antibody positive and over 50 % develop viremia. CMV is suppressive to cellular immunity; therefore, it worsens the conditions of AIDS patients to form a vicious cycle.

14.3.2.2 Pathophysiological Basis

The pathophysiological findings include hypermyelohemia, edema and demyelination. The lesions are initially in the perivascular area, followed by fusion into flakes with adjacent lesions to cause myelomalacia or even necrosis-induced cavities. Blood vessels in the lesion area enlarge, with infiltration of peripheral granular cells, inflammatory cells and gliocytes. The vascular endothelium is swollen to occlude some vessels. In the advanced stage, the spinal cord obviously shrinks, with accompanying gliosis and scars following myelomalcia.

14.3.2.3 Clinical Symptoms and Signs

Patients with CMV infection have symptoms of fever, headache, general upset, skin rash and involvement of some organs. The impaired spinal cord commonly causes incomplete flaccid paralysis or paraplegia.

14.3.2.4 Examinations and Their Selection

Laboratory Tests

CSF cytological changes should be observed and culture of CSF after its isolation should be performed. And PCR technology facilitates the diagnosis.

Diagnostic Imaging

MR imaging can define the size, shape and location of the foci as well as their relationship with the surrounding tissues. But the MRI demonstrations are not characteristic of CMV infection. The diagnosis should based on incorporation of the case history.

14.3.2.5 Imaging Demonstrations

CT Scanning Demonstrations

Lesions in the cervical and lumbar spinal cord is common, non-AIDS patients with cervical thoracic is common. CT scan shows mildly thickened spinal cord and uneven density spinal cord.

MR Imaging Demonstrations

MRI demonstrations are not specific, commonly thickened singular or multiple segments of the spinal cord, irregular long T1 and T2 signals in the spinal cord. Enhanced imaging commonly demonstrates no enhancement of the foci.

Case Study

A male patient aged 50 years was confirmatively diagnosed as having AIDS by CDC. The onset of the illness is acute and sudden. Viral retinitis occurred suddenly 2 weeks ago, causing rapidly decreased vision that progresses into blindness, with companying lower extremities numbness and weakness, unsmooth urine and dry stool. Three days ago, he suddenly developed paralysis, with urinary and fecal incontinence. His CD4 T cell count was 50/μl.
Fig. 14.5

(a, b) HIV/AIDS related CMV myelitis. (a, b) MR imaging demonstrations swollen lumbar spinal cord, long T1 and T2 signal in the spinal cord (arrow)

14.3.2.6 Criteria for Diagnosis

  1. 1.

    Clinical manifestations include lower extremities numbness and weakness, sudden attack of paralysis as well as urinary and fecal incontinence.

     
  2. 2.

    After CSF cytological test, isolation and culture of CSF and PCR, only half of the clinically typical cases have positive findings in cell culture.

     

14.3.2.7 Differential Diagnosis

HIV/AIDS related CMV myelitis should be differentiated from neoplasms of the spinal cord. The neoplasms commonly have slow progressions, with accompanying hemorrhage and necrosis of the neoplasms in uneven enhancement. CMV myelitis has sudden and acute onset, with no enhancement or even enhancement of the foci.

14.4 HIV/AIDS Related Spinal Bacterial Infection

14.4.1 Staphylococcus Aureus Infection

14.4.1.1 Pathogen and Pathogenesis

Spinal staphylococcus aureus infection is commonly caused by infections secondary to acute epidural or subdural abscess. It may also be caused by direct bacterial infection of the spinal cord. No matter of the primary or secondary infection, primary foci or primary history of infection commonly occur before the symptoms of the spinal cord, including septicemia, abscess of adjacent tissues and pyogenic infection of lungs. They are usually caused by attack of bacteria into the spinal cord and pia matter along with blood flow.

14.4.1.2 Pathophysiological Basis

The pathological changes vary with the routes of bacterial invasion. For those with local invasion by the bacteria, the lesions of spinal cord are confined within several spinal segments. For those with invasion by contaminated blood, multiple or disseminated foci commonly occur, mostly in the thoracic and lumbar area. By anatomy, it may be found to have swollen spinal cord, congestion and edema of the involved blood vessels, purulent secretions in the involved area, obviously thickened meninges, inflammatory effusion and granuloma formation. In addition, congestion and effusion of adjacent and supplying blood vessels occurs with thickened vascular walls to cause vascular occlusion. In the early stage of the inflammation, the spinal cord is congested with edema, followed by purplish gray and soft spinal cord, necrosis in the advanced stage. Its incision indicates scattered small foci of myelomalacia in the spinal tissues. Under a microscope, congestion of meningeal blood vessels can be found, with degeneration or obliteration of spinal neurons, dissolution of neuron axons, degeneration and loss of myelin. In addition, there is infiltration of disseminated inflammatory cells as well as proliferation of phagocytes and gliocytes. Multiple small abscesses in the spinal cord may integrate themselves into larger abscesses and massive necrosis of neural tissues. Purulent myelitis secondary to epidural or subdural abscess mainly demonstrates thickened and adhesion of meninges as well as vascular occlusion. The involved spinal cord is characterized by infiltration of inflammatory cells and ischemic necrosis. Upwards and downwards conductive bundles in the spinal cord can degenerate due to insufficient supply of nutrients by neuron axons.

14.4.1.3 Clinical Symptoms and Signs

Prior to onset of myelitis symptoms, patients usually exhibit toxic symptoms including high fever and chills. Several days later, complete or incomplete paraplegia may occur, with dysfunction urination and defecation. The location of lesions is commonly thoracic segment of the spinal cord, followed by the lumbar segment. The location of the lesions usually has the sensations of pain and girdling, with general muscular soreness.

14.4.1.4 Examinations and Their Selection

Laboratory Tests

Early blood culture is commonly positive. CSF is transparent or yellowish, with increased cells that are mainly neutrophils. It is commonly found to have increased protein, decreased glucose and chlorides and unobstructed vertebral canal. CSF smears or culture can detect the pathogens and the results of drug sensitivity test can provide basis for its treatment.

Diagnostic Imaging

CT scanning and MR imaging can define the size, shape and location of the foci as well as their relationship with the surrounding tissues.

14.4.1.5 Imaging Demonstrations

Imaging demonstrations of staphylococcus aureus myelitis is not characteristic, similar to other non-infective inflammations and demyelination. Plain CT scanning demonstrates locally thickened spine cord with irregular shapes, clearly defined borderline of the focus. For cases with abscess, enhanced CT scanning reveals ring shaped enhancement of the abscess wall. T2WI of MR imaging demonstrates confined or disseminated high signals within the spinal cord, with or with no space occupying effects. Enhanced MR imaging demonstrates diffusive, flaky and ring shaped enhancement. After the formation of abscess, the abscess wall demonstrates long T1 and short T2 signals and its inside abscess demonstrates long T1 and T2 signals. Enhanced T1W1 demonstrates ring shaped enhancement of the abscess wall and compressed thinner spinal cord.

Case Study

A male patient aged 48 years was confirmatively diagnosed as having AIDS by CDC. The illness was progressively severe, with lower extremities weakness as well as urinary and fecal incontinence for over 1 month. The sensory level of T10–T12 decreased, with grade III right muscle strength, grade II left muscle strength and positive muscular reflex. By bacteria culture, staphylococcus aureus infection was indicated.
Fig. 14.6

(a, b) HIV/AIDS related spinal bacterial infection. (a, b) MR imaging demonstrates abnormal strip liked long T1 and T2 signal in the vertebral canal of thoracic and lumbar segments. Enhanced imaging demonstrations of grid liked enhancement of the paraspinal abscess wall, and obviously compressed spinal cord

14.4.1.6 Criteria for the Diagnostic

  1. 1.

    Clinical manifestations include a history of general or local infection, with sudden onsets of paralysis, urination and defecation dysfunction as well as high fever.

     
  2. 2.

    Increased cell count and protein in CSF, decreased glucose and chloride and unobstructed spinal canal, which can facilitate the diagnosis

     
  3. 3.

    MR imaging demonstrates strip liked abnormal long T1 and T2 signals within thoracic and lumbar spinal canal; enhanced imaging demonstrates ring shaped or grid shaped enhancement of paravertebral abscess wall and obviously compressed spinal cord.

     

14.4.1.7 Differential Diagnosis

Acute Epidural Abscess

It develops 3–4 weeks after acute bacterial infection, with companying evident and severe nerve root pain and obvious spinal tenderness. Lumbar puncture suggests Queckenstedt test positive, yellowish CSF and increased proteins. Myelography indicates canal blockage, which should be further differentiated. If necessary, MRI examination can be performed to define the location and size of the abscess.

Tuberculosis Myelitis and Tuberculosis Paravertebral Abscesses

It has a chronic onset, with no accompanying fever or with accompanying low grade fever after noon. For cases with complication of tuberculosis abscess, the illness has an acute onset. However, the spinal cord commonly has kyphosis and obvious local tenderness. Plain chest X-ray demonstrates vertebral bone destruction, narrowed intervertebral space in angular deformity. Lumbar spinal puncture indicates obstructed spinal canal. The CSF test shows decreased glucose and chloride and increased protein. These findings are characteristic for differential diagnosis.

14.5 HIV/AIDS Related Vacuolar Myelopathy

Vacuolar myelopathy (VM) or chronic progressive myelopathy (CPM) is the most common primary infections of the nerve system in patients with AIDS. About 1/3 patients with AIDS suffer from vacuolation of the spinal white matter. By autopsy, 20–30 % cases have such an illness. However, its symptoms show up in cases with vacuolation and evident demyelination.

14.5.1 Pathogen and Pathogenesis

The pathogen and pathogenesis of vacuolar myelopathy (VM) is still unknown. Although findings of HIV by culture of the spinal cord have been reported [1], it has not been clarified whether HIV is the direct pathogen of VM. It is speculated that abnormal transmethylation induced by HIV or cytokine is the possible cause of VM.

14.5.2 Pathophysiological Basis

VM is pathologically typical of vacuoles in the spinal white matter, with invasion to the lateral and posterior columns, especially the thoracic spinal cord. It is commonly companied with spinal swelling or demyelination.

14.5.3 Clinical Symptoms and Signs

The clinical manifestations include progressive spastic paraplegia with accompanying deep sensation disturbance and sensory ataxia. The majority of such patients are bound to wheelchairs in weeks or months and minorities of such patients undergo painless progression in several years. Some patients also have vacuolar changes in the brain, with clinical manifestations of progressive dementia. Spinal spasticity rarely occurs.

14.5.4 Examinations and Their Selection

14.5.4.1 Electrophysiological Examination

Asymptomatic sub-acute spinal diseases can be detected in the early stage.

14.5.4.2 MR Imaging

MR imaging has no specific demonstrations, but can accurately locate the lesions.

14.5.5 Imaging Demonstrations

MR imaging commonly demonstrates long T1 and T2 signals of the lesions as well as myelatrophy.

14.5.6 Criteria for the Diagnosis

  1. 1.

    Clinical manifestations are progressive spastic paraplegia, wit accompanying deep sensation disturbance and sensory ataxia.

     
  2. 2.

    The diagnosis should exclude the possibility of compressive myelopathy, sub-acute combined degeneration and secondary infection.

     
  3. 3.

    MR imaging demonstration is commonly myelatrophy.

     

14.5.7 Differential Diagnosis

14.5.7.1 Differential Diagnosis from Toxoplasmosis

As an opportunistic infection, toxoplasmosis is commonly found in patients with compromised immunity. But simple toxoplasmosis is rarely seen. Most patients have motion disorder, especially the dismal lower extremities, which progresses into paraplegia. The sensory disturbance is commonly bilateral, with detectable sensory level in physical examinations. The common symptoms also include local pain, urinary disturbance and fever. Moreover, protein in CSF significantly increases with positive findings of serum toxoplasma antibody. Spinal MR imaging demonstrates intraspinal confined foci, which demonstrate enhancement by enhanced imaging. Most patients are sensitive to antibiotics therapies, with improved conditions.

14.5.7.2 Differential Diagnosis from Subacute Combined Myelopathy

Subacute combined myelopathy is commonly found in the thoracic spine. Plain CT scanning and enhanced scanning demonstrate no positive findings. MR imaging is the unique method for its detection. The imaging demonstrations include long strip liked equal T1 and long T2 signals of the posterior and lateral cords of the spine. Generally, there is no enhancement as well as thickened and swollen spinal cord, presenting difficulty in its differential diagnosis. For cases with anemia and decreased level of B12, diagnosis can be established.

14.5.7.3 Differential Diagnosis from Syringomyelia

Syringomyelia is congenital, with other complicated congenital abnormalities, such as spina bifida, spinal fusion and Arnold-Chiari malformation, which make it easy to be differentiated from VM. For cases with syringomyelia secondary to spinal neoplasms, spinal trauma, spinal hemorrhage or arachnoiditis, the case history, clinical manifestations and laboratory tests should be combined for its differential diagnosis from VM.

14.6 HIV/AIDS Related Myelatrophy

14.6.1 Pathogen and Pathogenesis

Ischemia of AIDS patients is a chronic progressive course. Due to angiotropic nature of HIV, its invasion to supplying arteries of spinal cord leads to endothelial granuloma of the supplying arteries and vascular lumen stenosis. Thereby, ischemia of spinal cord is caused to finally develop into myelatrophy.

14.6.2 Pathophysiological Basis

The pathological changes of myelatrophy are thinner spinal cord, dilated central canal of several segments and of the whole spinal cord in rare cases.

14.6.3 Clinical Symptoms and Signs

Clinical manifestation is motor and sensory disturbance of the corresponding spinal levels.

14.6.4 Examinations and Their Selection

Both CT scanning and MR imaging are important ways for the diagnosis of myelatrophy, with MR imaging being more accurate and convenient. Sagittal T1WI can directly demonstrate the range and severity of myelatrophy.

14.6.5 Imaging Demonstrations

MRI examination is the imaging of choice. Sagittal T1WI can directly demonstrate the range and severity of myelatrophy, which is commonly limited to several segments and rarely involves the whole spinal cord. There are intact appearance, possible dilation of central canal, widened subarachnoid space and often normal signals in the spinal cord.

Case Study 1

A male patient aged 34 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 10/μl.
Fig. 14.7

(ac) HIV/AIDS related myelatrophy. (ac) Sagittal T1WI and T2WI demonstrate the thinner spinal cord and widened subarachnoid space

Case Study 2

A male patient aged 30 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 35/μl.
Fig. 14.8

(ah) HIV/AIDS related myelatrophy. (ad) Sagittal T1WI and T2WI demonstrate thinner cervical spinal cord and widened subarachnoid space. (e, f) Sagittal T1WI and T2WI demonstrate thinner thoracic spinal cord and widened subarachnoid space. (g, h) Sagittal T1WI and T2WI demonstrate the thinner lumbar spinal cord and widened subarachnoid space

14.6.6 Criteria for the Diagnosis

  1. 1.

    It is clinically manifested as motor and sensory disturbance of the corresponding spinal levels.

     
  2. 2.

    MR imaging suggests myelatrophy.

     

14.6.7 Differential Diagnosis

HIV/AIDS related myelatrophy should be differentiated from myelatrophy caused by trauma, vascular malformation and myelitis. The diagnosis can be clarified in combination of the case history and imaging demonstrations.

14.7 HIV/AIDS Related Peripheral Neuropathy

14.7.1 HIV/AIDS Related Sensory Neuropathy

HIV/AIDS related sensory neuropathy is the most important HIV/AIDS related neuropathy, characteristic of the advanced stage of AIDS. About 45 % patients with AIDS have such an illness, but children with it are rarely found. Its pathogenesis remains unclear, which might be related with HIV or CMV infections. Pathological changes are macrophage infiltration in the peripheral nerves of the patients.

In the early stage of the infection, the temperature of both lower extremities slightly decreases, with no ankle reflex or decreased ankle reflex. The patients have no symptoms or slight symptoms. With the progression of the illness, tingling or numbness of the feet occurs, with the sensation extending to the knees. Both hands are rarely involved, but with occasionally obvious weakness of the extremities. In some patients, painful distal sensory neuropathy may occur, with its progression into the condition of difficulty walking. Electrophysiology, electromyography and sural nerve biopsy can facilitate its diagnosis.

14.7.2 HIV/AIDS Related Autonomic Neuropathy

A minority of patients may develop autonomic neuropathy in the advanced stage of HIV infection, with clinical manifestations of postural hypotension, diarrhea and sudden attack of arrhythmia. The sub-clinical autonomic neuropathy has an occurrence of 50 % in patients with advanced HIV infection. Autonomic neuropathy is usually accompanied by sensory neuropathy. Electrophysiology, electromyography and sural nerve biopsy can facilitate its diagnosis.

14.7.3 Human Cytomegalovirus Myelopathy (HCMV)

14.7.3.1 Pathogen and Pathogenesis

HCMV usually occurs in patients with CD4 T cell count being less than 0.1 × 109/L. In patients with their CD4 T cell counts being less than 0.05 × 109/L, the occurrence of HCMW is 30–40 %. Once the virus gains their access to the cells, the envelope of the virus adheres to the cell membrane and the viral genome integrates with the host cell nucleus. In cases with immature or compromised immunity, primary HCMV, reactivation of the latent virus or the newly emerging HCMV virus strain can cause massive duplication of the virus. Therefore, damages and diseases are resulted in. Most cases of HCMV are caused by reactivation of latent viruses.

14.7.3.2 Pathophysiological Basis

HCMV is pathologically characterized by arachnoid thickening, minor vessel dilation, a few lymphocytes infiltration, loosen and swollen spinal cord with disseminated small necrotic foci. Within the foci, 1–10 cytomegalic inclusions can be found, with no inflammatory responses in the surrounding tissues of the foci. Nervous system infected by cytomegalic inclusions demonstrates disseminated and nodular infiltration, with involvement of the nerve cells, especially obvious in the medullary olivary nucleus.

14.7.3.3 Clinical Signs and Symptoms

HCMV mainly invades the lower extremities, with accompanying myelopathies. Patients usually complain of ascending numbness of lower extremities, with companying weakness of both lower extremities and backache. Sometimes, sensory loss of sellar region occurs, with its progression into urination dysfunction. With the symptoms develop for days or weeks; the loss of deep tendon reflex occurs, with loss of distal sensation and accompanying weakness of the lower extremities and occasional occurrence of hand lesions.

14.7.3.4 Examinations and Their Selection

Laboratory Tests

CSF test has findings of increased cell count, mainly multinuclear leukocytes. Virus culture is negative, but positive in antibody or DNA assays.

Imaging Examinations

Imaging examinations are used to exclude the space occupying lesions of the lower spinal cord or the nerve root.

14.7.3.5 Imaging Demonstrations

Thoracic and lumbar MR imaging demonstrates swelling and aggregative changes of the cauda equine.

14.7.3.6 Criteria for the Diagnosis

  1. 1.

    CSF tests of CMV culture, antibody staining or DNA assay are positive.

     
  2. 2.

    Clinical manifestations are ascending numbness of lower extremities with weakness of both legs and urinary dysfunction. The loss of deep tendon reflex of legs occurs, with distal sensation loss and weakness of both legs.

     
  3. 3.

    MR imaging demonstrates swelling and agglutinative cauda equine.

     

14.7.3.7 Differential Diagnosis

The condition should be differentiated from varicella zoster virus (VZV) myelitis, which has a sub-acute onset. Patients with VZV myelitis commonly have a case history of VZV infection. By CSF test, there are increased protein, motor/sensory disturbance, sphincter dysfunction and lesions of the skin innervated by corresponding nerve system. Myelitis generally occurs 2–3 weeks after skin rash, with nerve lesions of the thoracic segment. The differential diagnosis should be based on the combination of case history and skin lesions.

Case Study

The female patient aged 31 years was confirmatively diagnosed as having AIDS by CDC. Her CD4 T cell count was 25/μl.
Fig. 14.9

HIV/AIDS related CMV myelitis. Sagittal T2WI demonstrates L2–L4 spinal cord lesions, paravetebral mass shadows with heterogeneous signals and enlarged masses with its extra-epidural part (arrow)

14.7.4 Compound Mononeuritis

Compound mononeuritis occurs in a minority of AIDS patients in its advanced stage. The illness occurs when CD4 T cell count is no less than 0.25 × 109/L (250/mm3). Compound mononeuritis can also be caused by CMV when CD4 T cell count is below 0.05 × 109/L (50/mm3). For cases with CD4 T cell count above 200/μl, neural biopsy demonstrates axon degeneration and peripheral inflammatory infiltration of blood vessels. For patients in the advanced stage, neural biopsy demonstrates compound demyelination and axon degeneration, with accompanying macrophage infiltration characteristic of CMV infection. The diagnosis of compound mononeuritis usually depends on the clinical manifestations. Electromyelography suggests multiple local axon neuropathies. By CSF, the findings are non-specific, only with an increase of protein and a slight increase of monocytes. The imaging demonstrations are also non-specific.

14.7.5 Distal Symmetrical Polyneuropathy (DSPN)

DPSN is also known as progressive peripheral neuropathy, characterized by delayed sensation of pain. Such patients have moderate loss of symmetrical distal sensation or numbness, burning sensation and itches. These symptoms initially occur in hands and feet with a stock liked or glove liked distribution. Physical examination demonstrates loss of warm and painful sensation of hands and feet, loss or decreased ankle reflex, weakness and shrinkage of distal muscles. CSF test indicates normal or an increase of proteins. Electromyelography and nerve conduction velocity usually indicate distal sensory and motor evidence of neuropathy characteristic of demyelination and mild nerve conduction deceleration. This disease is predominant of delayed and decreased painful sensation, occasional with mild distal weakness and decreased or loss of ankle reflex. Neural pathological examination demonstrates axon degeneration, occasional segmental demyelination, which is closely related with AIDS.

The diagnosis of HIV/AIDS related DPSN is based on detailed case history in neurology and physical examinations. Laboratory tests can be used to exclude the potential causes of neuropathy, including diabetes, vitamin deficiency, hereditary factors and other infections. Electromyelography, CSF test and biopsy can facilitate the diagnosis.

14.7.6 Multiple Mononeuropathy

Multiple mononeuropathy demonstrates cerebral nerve involvement, distal symmetrical or asymmetrical neuropathy. The involved areas innervated by nerves have motor or sensory deficiency. The pathological findings include segmental demyelination of the peripheral nerves and/or axon degeneration. CSF test indicates normal or a mild increase of protein and an increase of IgG potency. Electromyelography suggests axonal multi-neuropathy. Neural biopsy can provide accurate evidence for the determination of the nature and degree of neural injuries.

14.7.7 Chronic Infectious Demyelinating Polyneuropathy (CIDP)

CIDP occurs with an acute onset when serum HIV antibody inverts positive or with a chronic onset in the advanced stage of AIDS with mild immunodeficiency. Local lesions are loss or thinner myelin sheath, decreased myelinated nerve fibers, distribution of proliferated Schwan cells in concentric circles like onions and lymphocytes infiltration. Lesions can be found in spinal nerves and proximal nerve trunk. Demyelination and regeneration of nerves roots and trunks as well as lymphocytes infiltration can cause painful extremities, exercise fatigue, decreased tendon reflex and sensory disturbance. CSF test shows increased protein and lymphocytes and an increase of globulin potency. The diagnosis of CIDP can be made based on the symptoms and signs, CSF and electrophysiology. The definitive diagnosis sometimes needs nerves biopsy.

Case Study 1

A male patient aged 51 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 45/μl.
Fig. 14.10

(ad) HIV/AIDS related CIDP. (a, b) Plain T1WI imaging of HIV/AIDS related CIDP. (c, d) Enhanced T1WI imaging demonstrates enhancement of intrathecal nerve roots

Case Study 2

A male patient aged 42 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 65/μl.
Fig. 14.11

(a, b) HIV/AIDS related CIDP. (a, b) Enhanced sagittal T1WI imaging demonstrates agglutinative nerves of cauda equian and their nodular enhancement (arrow)

Case Study 3

A male patient aged 34 years was confirmatively diagnosed as having AIDS by CDC. His CD4 T cell count was 25/μl.
Fig. 14.12

(a, b) HIV/AIDS related CIDP. (a) T1WI scanning. (b) Enhanced T1WI imaging demonstrates enhanced swollen nerve roots (arrow)

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Copyright information

© Springer Science+Business Media Dordrecht and People’s Medical Publishing House 2014

Authors and Affiliations

  • Hongjun Li
    • 1
  1. 1.Radiology Department Beijing You’an HospitalCapital Medical UniversityBeijingPeople’s Republic of China

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