1. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions HIV Neuropathy and Myelopathy Sam Nightingale Sam Nightingale is a neurology registrar and MRC clinical research fellow. He is currently working with the Liverpool HIV Pharmacology Group and the Liverpool Brain Infections Group on studies of the CNS penetration of antiretroviral drugs for HIV. Edited by Prof Tom Solomon, Dr Agam Jung and Dr Sam Nightingale This session provides an overview of the peripheral nervous system effects of HIV infection and antiretroviral therapy.

2. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Learning Objectives By the end of this session you will be able to: State the causes of peripheral nerve damage in HIV List the medications used in HIV that commonly cause peripheral nerve damage Summarise the clinical features of nerve damage associated with the following: antiretroviral treatment, chronic HIV infection and HIV seroconversion Describe an appropriate strategy for diagnosing and investigating an HIV positive individual presenting with painful numb feet List the treatment and symptomatic management options for HIV-associated peripheral sensory neuropathy

3. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Introduction Although there has been a decline in opportunistic infections related to HIV, the prevalence of peripheral neuropathy has increased due to improved longevity and the use of neurotoxic medications. Symptomatic peripheral neuropathy occurs in 30-50% of those in the late stages of HIV, however pathological changes in the nerves can be demonstrated in nearly all. Although most common in advanced disease, neuropathy can occur at any stage. It may be related to: The HIV virus itself Neurotoxic medications Nutritional deficiencies Alcohol excess Autoimmune demyelination Opportunistic infections such as CMV, hepatitis C or syphilis

4. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions The most common peripheral nerve disorder encountered due to HIV is a distal sensory peripheral neuropathy (DSPN), sometimes called distal symmetrical sensory polyneuropathy (DSSP) or distal painful sensorimotor neuropathy (DPSN). DSPN usually becomes symptomatic in the later stages of infection when the CD4 count is below 200 cells/ml. However, it is not an AIDS defining illness in itself. Distal Sensory Periperal Neuropathy/DSPN The risk of developing DSPN is higher if there are other neuropathic risk factors, such as diabetes, excess alcohol intake, nutritional/vitamin deficiencies and genetic neuropathies.

5. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions. Pathophysiology Neurones are damaged by direct HIV infection, as well as by locally infiltrating activated macrophages that secrete neurotoxic cytokines or other toxic metabolites. This process causes axonal degeneration with some demyelination. Histologically there is prominent perivascular infiltration by T-cells and macrophages and mild loss of dorsal root ganglion neurons, some of which are directly infected with HIV as demonstrated by in situ PCR.

6. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Symptoms and Signs The typical presentation is painful numb feet in an individual in the late stages of HIV infection or AIDS. Significant weakness is unusual and the upper limbs are rarely involved. Symptoms progress slowly over the course of months to years. Although pain is not universal, 30-50% complain of burning or stabbing pain. This can be quite disabling and sometimes even makes walking difficult. Small sympathetic and parasympathetic nerve fibres can also be affected, causing dizziness due to postural hypotension, impaired bladder and bowel control and erectile dysfunction. The neurological signs are characteristic of a small fibre neuropathy. Decreased vibration sense at the toe or ankle, decreased sensitivity to pain and temperature in a stocking distribution, and depressed or absent ankle reflexes. Proprioception is usually normal. Weakness and wasting is usually mild and atrophy of intrinsic foot muscles is rarely a prominent feature. Upper limb involvement usually only occurs when the lower limb features are advanced.

7. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Diagnosis Nerve conduction studies can show mild axonal damage, but may fail to demonstrate any abnormality. Thermal thresholds, which are raised with small fibre damage, are usually abnormal. Blood glucose, vitamin B12 and folate should be checked to exclude common reversible causes of neuropathy. However, if clinical features are typical of DSPN, further investigation may not be necessary. The presence of upper limb or trunk involvement, significant lower limb weakness or decreased proprioception should prompt investigation for other disorders. Nerve biopsy may be required to exclude vasculitis, demyelination or lymphomatous infiltration. Abnormalities rarely effect the upper limbs unless disease is very advanced

8. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions A dose dependent peripheral neuropathy occurs in about 10-30 % of patients treated with didanosine (ddI), zalcitabine (ddC) or stavudine (d4T). These nucleoside reverse transcriptase inhibitors (NRTIs) are known collectively as dideoxynucleoside agents or 'd-drugs'. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and other NRTIs are not generally associated with a peripheral neuropathy. Drug related toxic neuropathy is indistinguishable from HIV induced DSPN, both on clinical and neurophysiological grounds. The two conditions frequently co-exist. Presentation is the same as DSPN with a distal, symmetrical, predominantly lower limb, predominantly sensory, often painful, axonal neuropathy Medication related toxic neuropathy I

9. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions After stopping the offending medication, neuropathic symptoms may worsen for 4–8 weeks (sometimes referred to as 'coasting') after which symptoms improve, although recovery can be slow and residual nerve damage is not uncommon. In some cases incomplete resolution may be due to coincident DSPN. The underlying mechanism may be mitochondrial toxicity from inhibition of DNA polymerase. The same mechanism could also account for the other side effects with this class of 'd drugs' e.g. pancreatitis, fulminant hepatic failure and lactic acidosis. Serum lactate is elevated in over 90% of patients with 'd-drug' related neuropathy. Medication related toxic neuropathy II Electron microscopy showing mitochondria in pancreatic tissue.

10. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Other Drug Treatments In addition to antiretrovirals, several other drugs used in the treatment of HIV can cause neuropathy. These include: Dapsone -used in the treatment of pneumocystis jiroveci pneumonia Isoniazid - used in the treatment of TB, can cause B6 deficiency Metronidazole – used in the treatment of amoebic dysentery and microsporidiosis Vincristine – used in the treatment of Kaposi's sarcoma and non – Hodgkin's lymphoma Thalidomide – used in the treatment of various cancers, wasting syndrome and severe mouth ulcers.

11. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Demyelination I Although many of the complications of HIV are related to immunodeficiency, there is also a general state of immune activation, which can result in autoimmunity, with T-cell activation and hypergammaglobulinemia. As such, HIV infection is an important cause of inflammatory demyelinating neuropathies such as Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP).

12. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Demyelination II Guillain-Barré Syndrome (GBS)/Acute Inflammatory Demyelinating Polyneuropathy HIV infection should be excluded in any patient presenting with GBS as it can be clinically indistinguishable from GBS in HIV-seronegative individuals. It usually occurs at primary infection or seroconversion, but is rarely associated with immune reconstitution. The typical clinical presentation is an areflexic, symmetrical ascending weakness with relatively little sensory involvement. Cranial neuropathies and involvement of respiratory muscles can lead to respiratory or pharyngeal insufficiency. Autonomic involvement can cause cardiac arrhythmias and severe fluctuations in arterial blood pressure. These possible life-threatening complications require close monitoring. Symptoms progress over a maximum of four weeks, before spontaneous improvement. If there has been secondary axonal damage, recovery may be slow. Around 30% have varying degrees of residual disability. GBS due to HIV is associated with more frequent recurrent acute episodes and relapses than is seen in sero-negative individuals. CSF shows raised protein. In contrast to HIV-seronegative individuals, there is often a mild CSF pleocytosis, up to 50 cells/ml.

13. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Demyelination III Chronic, Inflammatory, Demyelinating Polyneuropathy (CIDP) Whereas GBS is an acute, self-limiting illness, CIDP is characterised by chronic progression over months, with periods of fluctuating weakness and sensory disturbance. As with GBS, CSF pleocytosis can help identify those with HIV infection. CIDP can occur at any stage of HIV infection. The reason for chronic persistence of the autoimmune demyelinating process is not known.

14. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Other Neuropathies I Vasculitic neuropathy A necrotizing vasculitis is a rare cause of neuropathy in HIV. It typically causes a mononeuritis multiplex, involving multiple individual nerves to different extents, rather than the length dependent neuropathy described earlier. The vasculitic process may also involve other organs such as heart, kidneys and muscle. Cryoglobulinaemia associated with hepatitis C co-infection can also also cause a vasculitic neuropathy. Diffuse Infiltrative Lymphocytosis Syndrome (DILS) An axonal neuropathy can occur in association with the DILS syndrome. This is a hyperimmune reaction against HIV characterised by a persistent CD8+ lymphocytosis and lymphocytic infiltration of various organs. The reported prevalence varies between 0.85 – 3%, and appears to be more common in Africans. Symptoms can resemble Sjögren's syndrome. Most patients present with bilateral parotid gland enlargement and features of the Sicca syndrome. Lymphadenopathy, splenomegaly, pneumonitis and renal dysfunction may occur. Therapeutic trials are lacking, although there can be a good response to antiretroviral and steroid therapy.

15. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Other Neuropathies II CMV Neuropathy CMV infection can cause an asymmetric axonal polyneuropathy in the late stages of HIV infection, usually at CD4 counts less than 100cells/ul and often with involvement of other organs. CMV encephalitis can also occur. CMV can be detected by PCR in the plasma and is present in the CSF in 90%. Treatment is with ganciclovir or foscarnet therapy. Relapse is common unless immune function can be improved. The image below shows a gross micrograph of a coronal slice of brain from a patient with HIV disease who has CMV ventriculitis (ependymitis). It shows dilated lateral ventricles adjacent to the basal ganglia. The lining of the ventricles (the ependyma) is reddened and inflamed.

16. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Other Neuropathies III Neuropathy Due to Other Diseases Syphilis should always be excluded by serology and there should be a low threshold for treatment. Tuberculosis or lymphoma affecting nerve roots, cauda equina or meninges can cause an acute or subacute polyradiculopathy with flaccid paraparesis of the lower limbs, bowel dysfunction and a sensory level. Other important causes of a neuropathy are alcohol abuse, diabetes mellitus and malnutrition, particularly in patients with malignancy, gastrointestinal diseases or wasting syndromes. The images below show cutaneous secondary syphilis.

17. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Treatment Discontinue neurotoxic drugs if possible. HIV should be treated with a fully suppressive regime and superimposed infections such as CMV treated appropriately. Intravenous immunoglobin and plasmapheresis may be required in GBS and CIDP depending on the severity. Poor nutrition needs addressing and if in doubt, vitamin supplements should be given. Alcohol should be avoided and high blood sugars controlled. Individuals with peripheral sensory neuropathy should receive advice on foot care to avoid painless injury to numb toes or feet.

18. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Treatment II Pain Relief Pain can be a big problem in HIV infection. 80% of HIV infected individuals with pain receive inadequate analgesia compared with 40% with cancer. This may be due to stoicism and reluctance to report symptoms or the stigma of substance abuse. Neuropathic pain can be managed with anticonvulsants, antidepressants, analgesics and topical treatments, however neuropathic pain is notoriously refractory to treatment. Gabapentin tends to be first line and Lamotrigine has been shown to be effective in HIV neuropathy. Pregabalin and Amitriptyline are used because of their effectiveness in diabetic neuropathy, although a small trial of Amitriptyline in HIV neuropathy failed to show benefit. Topical analgesics Capsaicin and Lignocaine patch have demonstrated efficacy.

19. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions HIV associated Myelopathy I HIV myelopathy is most common in those with advanced immunosuppression and often coincides with neurocognitive symptoms. Before antiretroviral therapy, HIV myelopathy was seen in up to 20% but is now much less common. In contrast to HIV encephalopathy, astrocytes and neurons do not appear to be directly infected and the exact mechanism of damage is not clear. Post-mortem histology shows vacuoles with lipid-laden macrophages in the spinal cord, so HIV myelopathy is often referred to as 'vacuolar myelopathy'. Although such features are common at autopsy, much fewer have clinically evident myelopathy during life.

20. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions HIV associated Myelopathy II Myelopathy typically presents in the legs with a slowly progressive symmetrical weakness, stiffness and sensory loss and sphincter dysfunction. There may be signs of spasticity with increased tone, hyper-reflexia and extensor plantar responses. Limbs may be numb or dysaesthetic, but as the damage is diffuse in HIV myelopathy, a discrete sensory level is unusual and suggests a different cause. Imaging with MRI is often normal, or may show non- specific features such as spinal cord atrophy or diffuse non-enhancing high signal area

21. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions HIV associated Myelopathy III CSF examination is usually normal, or has non-specific abnormalities, such as a raised white cell count (up to 50 cells/μl). HIV myelopathy is a diagnosis of exclusion. Imaging and lumbar puncture are important to rule out other causes of myelopathy, such as:. Spinal cord compression Sub-acute combined degeneration of the cord due to B12 deficiency Infections with cytomegalovirus, varicella-zoster virus, herpes simplex virus and HTLV-1 There is no specific treatment. Antiretroviral therapy may initially lead to significant improvement and may slow the usual disabling progression.

22. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Key Points Neuropathy in HIV is common and has a number of different causes. Most commonly neuropathy is due to HIV itself, or one of a number of neurotoxic medications used in HIV. These causes are clinically indistinguishable and frequently overlap. HIV infection can be associated with a Gullian-Barre Syndrome, particularly at seroconversion. HIV testing should be considered in all presenting with GBS. Specific treatment should be aimed at the underlying cause. HIV neuropathy is frequently painful and there are a number of symptomatic treatments.

23. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Summary Having completed this session you will now be able to: State the causes of peripheral nerve damage in HIV List the medications used in HIV that commonly cause peripheral nerve damage Summarise the clinical features of nerve damage associated with the following: antiretroviral treatment, chronic HIV infection and HIV seroconversion Describe an appropriate strategy for diagnosing and investigating a HIV positive individual presenting with painful numb feet List the treatment and symptomatic management options for HIV- associated peripheral sensory neuropathy References and Further Reading 1.Attala N et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European Journal of Neurology 2010;17: 1113–1123. 2.Simpson DM et al. Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology. 2010;74(5):413-20. 3.Simpson DM et al. HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology. 2006;66(11):1679-87. 4.Verma A. Epidemiology and clinical features of HIV-1 associated neuropathies. J Peripher Nerv Syst. 2001;6(1):8-13. 5.Simpson DM. Selected peripheral neuropathies associated with humanimmunodeficiency virus infection and antiretroviral therapy. J Neurovirol. 2002;8 Suppl 2:33-41.

24. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 1 Select the single best answer from the options given. Click on the answer to see if it is correct and read an explanation. A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyDistal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyDistal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyDistal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

25. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 1 INCORRECT Please select one of the alternative answers INCORRECT Please select one of the alternative answers A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyDistal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyDistal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

26. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 1 CORRECT Although we are not told what she has taken in the past, none of the antiretroviral medications she is currently taking commonly cause a neuropathy. Her low CD4 puts her at risk of DSPN. The diabetes is likely to be compounding the problem and sugars should be tightly controlled. How much of the problem is related to diabetes and how much to HIV is often difficult to determine accurately and both should be addressed. Click here to move on to the next question CORRECT Although we are not told what she has taken in the past, none of the antiretroviral medications she is currently taking commonly cause a neuropathy. Her low CD4 puts her at risk of DSPN. The diabetes is likely to be compounding the problem and sugars should be tightly controlled. How much of the problem is related to diabetes and how much to HIV is often difficult to determine accurately and both should be addressed. Click here to move on to the next question A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 37-year-old lady complains of numb feet. She has a constant burning sensation and they are painful to touch. She has been on ART for 12 years and currently takes Atripla (efavirenz/emtricitabine/tenofovir). Despite treatment her CD4 is 120 cells/ul. She is overweight and has recently been diagnosed with type 2 diabetes. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

27. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions A 45-year-old HIV positive man presents with numb feet and difficulty walking. He is poorly compliant with his ART and last CD4 count was 80 cell/ul. He drinks 15 units of alcohol/day and lives in a hostel. The hostel say he has has severe diarhoea for 6 months. On examination he is thin and unkempt. There is no sensation to light touch below the knee. Although ankle reflexes are absent, plantar responses are extensor. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 45-year-old HIV positive man presents with numb feet and difficulty walking. He is poorly compliant with his ART and last CD4 count was 80 cell/ul. He drinks 15 units of alcohol/day and lives in a hostel. The hostel say he has has severe diarhoea for 6 months. On examination he is thin and unkempt. There is no sensation to light touch below the knee. Although ankle reflexes are absent, plantar responses are extensor. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy Question 2

28. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 2 INCORRECT Please select an alternative answer INCORRECT Please select an alternative answer Click here to move on to the next question A 45-year-old HIV positive man presents with numb feet and difficulty walking. He is poorly compliant with his ART and last CD4 count was 80 cell/ul. He drinks 15 units of alcohol/day and lives in a hostel. The hostel say he has has severe diarhoea for 6 months. On examination he is thin and unkempt. There is no sensation to light touch below the knee. Although ankle reflexes are absent, plantar responses are extensor. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 45-year-old HIV positive man presents with numb feet and difficulty walking. He is poorly compliant with his ART and last CD4 count was 80 cell/ul. He drinks 15 units of alcohol/day and lives in a hostel. The hostel say he has has severe diarhoea for 6 months. On examination he is thin and unkempt. There is no sensation to light touch below the knee. Although ankle reflexes are absent, plantar responses are extensor. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

29. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions CORRECT It is likely that there are a number of causes for this mans neuropathy. Although his advanced immunosupression puts him at risk for DSPN, the absent ankle relexes with upgoing plantar suggest subacute combined degeneration of the cord. His poor diet and prolonged diarrhoea (likely HIV related) put him at risk of B12/folate deficiency. In addition he is likely to be thiamine deficient due to his alcoholism. Click here to move on to the next question CORRECT It is likely that there are a number of causes for this mans neuropathy. Although his advanced immunosupression puts him at risk for DSPN, the absent ankle relexes with upgoing plantar suggest subacute combined degeneration of the cord. His poor diet and prolonged diarrhoea (likely HIV related) put him at risk of B12/folate deficiency. In addition he is likely to be thiamine deficient due to his alcoholism. Click here to move on to the next question Question 2 A 45-year-old HIV positive man presents with numb feet and difficulty walking. He is poorly compliant with his ART and last CD4 count was 80 cell/ul. He drinks 15 units of alcohol/day and lives in a hostel. The hostel say he has has severe diarhoea for 6 months. On examination he is thin and unkempt. There is no sensation to light touch below the knee. Although ankle reflexes are absent, plantar responses are extensor. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 45-year-old HIV positive man presents with numb feet and difficulty walking. He is poorly compliant with his ART and last CD4 count was 80 cell/ul. He drinks 15 units of alcohol/day and lives in a hostel. The hostel say he has has severe diarhoea for 6 months. On examination he is thin and unkempt. There is no sensation to light touch below the knee. Although ankle reflexes are absent, plantar responses are extensor. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

30. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions A 26-year-old man presents feeling unwell with a flu like illness. Over the course of 2 days he develops rapidly progressive weakness of his legs and now has symptoms in his hands. He has no sensory symptoms but on examination he has loss of vibration sense to the knee. He is arefexic throughout. CSF is acellular with a raised protein. While on holiday one month previously he had unprotected sex, but had a HIV test which was negative. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 26-year-old man presents feeling unwell with a flu like illness. Over the course of 2 days he develops rapidly progressive weakness of his legs and now has symptoms in his hands. He has no sensory symptoms but on examination he has loss of vibration sense to the knee. He is arefexic throughout. CSF is acellular with a raised protein. While on holiday one month previously he had unprotected sex, but had a HIV test which was negative. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy Question 3

31. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 3 INCORRECT Select an alternative answer INCORRECT Select an alternative answer A 26-year-old man presents feeling unwell with a flu like illness. Over the course of 2 days he develops rapidly progressive weakness of his legs and now has symptoms in his hands. He has no sensory symptoms but on examination he has loss of vibration sense to the knee. He is arefexic throughout. CSF is acellular with a raised protein. While on holiday one month previously he had unprotected sex, but had a HIV test which was negative. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 26-year-old man presents feeling unwell with a flu like illness. Over the course of 2 days he develops rapidly progressive weakness of his legs and now has symptoms in his hands. He has no sensory symptoms but on examination he has loss of vibration sense to the knee. He is arefexic throughout. CSF is acellular with a raised protein. While on holiday one month previously he had unprotected sex, but had a HIV test which was negative. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

32. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 3 CORRECT This rapidly ascending weakness with relatively little sensory involvement is likely to be due to Guillan Barre Syndrome. The raised CSF protein supports this. This may be part of a HIV seroconversion illness. Although previously negative, the HIV test should be repeated as antibodies to HIV are absent prior to seroconverion. Seroconverion occurs when antibodies to HIV develop. This may occur 3 months or more after initial infection. There may be a CSF pleocytosis, however this is not universal, and HIV testing should be performed even if the CSF is acellular, as in this case. Click here to move on to the next question CORRECT This rapidly ascending weakness with relatively little sensory involvement is likely to be due to Guillan Barre Syndrome. The raised CSF protein supports this. This may be part of a HIV seroconversion illness. Although previously negative, the HIV test should be repeated as antibodies to HIV are absent prior to seroconverion. Seroconverion occurs when antibodies to HIV develop. This may occur 3 months or more after initial infection. There may be a CSF pleocytosis, however this is not universal, and HIV testing should be performed even if the CSF is acellular, as in this case. Click here to move on to the next question A 26-year-old man presents feeling unwell with a flu like illness. Over the course of 2 days he develops rapidly progressive weakness of his legs and now has symptoms in his hands. He has no sensory symptoms but on examination he has loss of vibration sense to the knee. He is arefexic throughout. CSF is acellular with a raised protein. While on holiday one month previously he had unprotected sex, but had a negative HIV test. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 26-year-old man presents feeling unwell with a flu like illness. Over the course of 2 days he develops rapidly progressive weakness of his legs and now has symptoms in his hands. He has no sensory symptoms but on examination he has loss of vibration sense to the knee. He is arefexic throughout. CSF is acellular with a raised protein. While on holiday one month previously he had unprotected sex, but had a negative HIV test. Select one answer from the list below. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

33. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions A 40-year-old lady with longstanding HIV presents with painful numb feet. She is taking Nevirapine/Stavudine/Tenofovir. As her HIV is well controlled on this regime it has not been changed. She has recently been diagnosed with pulmonary TB. Standard nerve conduction studies are normal but thermal thresholds are abnormal. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 40-year-old lady with longstanding HIV presents with painful numb feet. She is taking Nevirapine/Stavudine/Tenofovir. As her HIV is well controlled on this regime it has not been changed. She has recently been diagnosed with pulmonary TB. Standard nerve conduction studies are normal but thermal thresholds are abnormal. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy Question 4

34. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 4 Click here to move on to the next question INCORRECT Select an alternative answer INCORRECT Select an alternative answer A 40-year-old lady with longstanding HIV presents with painful numb feet. She is taking Nevirapine/Stavudine/Tenofovir. As her HIV is well controlled on this regime it has not been changed. She has recently been diagnosed with pulmonary TB. Standard nerve conduction studies are normal but thermal thresholds are abnormal. a. Distal sensory peripheral neuropathy (DSPN) a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyMedication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 40-year-old lady with longstanding HIV presents with painful numb feet. She is taking Nevirapine/Stavudine/Tenofovir. As her HIV is well controlled on this regime it has not been changed. She has recently been diagnosed with pulmonary TB. Standard nerve conduction studies are normal but thermal thresholds are abnormal. a. Distal sensory peripheral neuropathy (DSPN) a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathyMedication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

35. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 4 CORRECT The abnormal thermal thresholds are consistent with a small fibre neuropathy. This lady is taking Stavudine (d4T) a neurotoxic antiretroviral that is now rarely used in the west. She has recently been diagnosed with TB and her treatment will contain Isoniazid which is also neurotoxic. This combination is the likely cause of her neuropathy. Click here to move on to the next question CORRECT The abnormal thermal thresholds are consistent with a small fibre neuropathy. This lady is taking Stavudine (d4T) a neurotoxic antiretroviral that is now rarely used in the west. She has recently been diagnosed with TB and her treatment will contain Isoniazid which is also neurotoxic. This combination is the likely cause of her neuropathy. Click here to move on to the next question A 40-year-old lady with longstanding HIV presents with painful numb feet. She is taking Nevirapine/Stavudine/Tenofovir. As her HIV is well controlled on this regime it has not been changed. She has recently been diagnosed with pulmonary TB. Standard nerve conduction studies are normal but thermal thresholds are abnormal. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy A 40-year-old lady with longstanding HIV presents with painful numb feet. She is taking Nevirapine/Stavudine/Tenofovir. As her HIV is well controlled on this regime it has not been changed. She has recently been diagnosed with pulmonary TB. Standard nerve conduction studies are normal but thermal thresholds are abnormal. a. Distal sensory peripheral neuropathy (DSPN) b. Medication related toxic neuropathy c. Demyelination d. Nutritional deficiency e. Other cause of neuropathy

36. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 5. Which of the following medications used in HIV does not cause a neuropathy? a. Didanosine (ddI) b. Abacavir (ABC) c. Vincristine (Kaposi's sarcoma and non-Hodgkin's lymphoma) d. Zalcitabine (ddC) e. Dapsone (pneumocystis jiroveci pneumonia) Which of the following medications used in HIV does not cause a neuropathy? a. Didanosine (ddI) b. Abacavir (ABC) c. Vincristine (Kaposi's sarcoma and non-Hodgkin's lymphoma) d. Zalcitabine (ddC) e. Dapsone (pneumocystis jiroveci pneumonia)

37. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 5 Which of the following medications used in HIV does not cause a neuropathy? a. Didanosine (ddI) b. Abacavir (ABC) c. Vincristine (Kaposi's sarcoma and non-Hodgkin's lymphoma) d. Zalcitabine (ddC) e. Dapsone (pneumocystis jiroveci pneumonia) Which of the following medications used in HIV does not cause a neuropathy? a. Didanosine (ddI) b. Abacavir (ABC) c. Vincristine (Kaposi's sarcoma and non-Hodgkin's lymphoma) d. Zalcitabine (ddC) e. Dapsone (pneumocystis jiroveci pneumonia) INCORRECT Select an alternative answer INCORRECT Select an alternative answer

38. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 5 CORRECT answer. Click here to move onto the next question CORRECT answer. Click here to move onto the next question Which of the following medications used in HIV does not cause a neuropathy? a. Didanosine (ddI) b. Abacavir (ABC) c. Vincristine (Kaposi's sarcoma and non-Hodgkin's lymphoma) d. Zalcitabine (ddC) e. Dapsone (pneumocystis jiroveci pneumonia) Which of the following medications used in HIV does not cause a neuropathy? a. Didanosine (ddI) b. Abacavir (ABC) c. Vincristine (Kaposi's sarcoma and non-Hodgkin's lymphoma) d. Zalcitabine (ddC) e. Dapsone (pneumocystis jiroveci pneumonia)

39. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 5 Answer the following question by clicking on either true or false. The prevalence of neuropathy in HIV is decreasing. TRUE FALSE The prevalence of neuropathy in HIV is decreasing. TRUE FALSE

40. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 5 Answer the following question by clicking on either true or false. Sorry INCORRECT answer. Although there has been a decline in opportunistic infections related to HIV, the prevalence of peripheral neuropathy has increased due to improved longevity and the use of neurotoxic medications. Click here to move onto the next question Sorry INCORRECT answer. Although there has been a decline in opportunistic infections related to HIV, the prevalence of peripheral neuropathy has increased due to improved longevity and the use of neurotoxic medications. Click here to move onto the next question The prevalence of neuropathy in HIV is decreasing. TRUE FALSE The prevalence of neuropathy in HIV is decreasing. TRUE FALSE

41. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 5 Answer the following question by clicking on either true or false. CORRECT answer. Although there has been a decline in opportunistic infections related to HIV, the prevalence of peripheral neuropathy has increased due to improved longevity and the use of neurotoxic medications. Click here to move onto the next question. CORRECT answer. Although there has been a decline in opportunistic infections related to HIV, the prevalence of peripheral neuropathy has increased due to improved longevity and the use of neurotoxic medications. Click here to move onto the next question. The prevalence of neuropathy in HIV is decreasing. TRUE FALSE The prevalence of neuropathy in HIV is decreasing. TRUE FALSE

42. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 6 Answer the following question by clicking on either true or false. DSPN is an AIDS defining illness TRUE FALSE DSPN is an AIDS defining illness TRUE FALSE

43. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 6 Answer the following question by clicking on either true or false. Sorry INCORRECT answer. DSPN usually becomes symptomatic in the later stages of infection when the CD4 count is below 200/μl. However, it is not an AIDS defining illness in itself. Click here to move onto the next question Sorry INCORRECT answer. DSPN usually becomes symptomatic in the later stages of infection when the CD4 count is below 200/μl. However, it is not an AIDS defining illness in itself. Click here to move onto the next question DSPN is an AIDS defining illness TRUE FALSE DSPN is an AIDS defining illness TRUE FALSE

44. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 6 Answer the following question by clicking on either true or false. CORRECT answer. DSPN usually becomes symptomatic in the later stages of infection when the CD4 count is below 200/μl. However, it is not an AIDS defining illness in itself Click here to move onto the next question. CORRECT answer. DSPN usually becomes symptomatic in the later stages of infection when the CD4 count is below 200/μl. However, it is not an AIDS defining illness in itself Click here to move onto the next question. DSPN is an AIDS defining illness TRUE FALSE DSPN is an AIDS defining illness TRUE FALSE

45. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 7 Answer the following question by clicking on either true or false. Nerve conduction studies are almost always abnormal in medication related toxic neuropathy TRUE FALSE Nerve conduction studies are almost always abnormal in medication related toxic neuropathy TRUE FALSE

46. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 7 Answer the following question by clicking on either true or false. Sorry INCORRECT answer. Nerve conduction studies can show mild axonal damage, but may fail to demonstrate any abnormality. Thermal thresholds, which are raised with small fibre damage, are usually abnormal Click here to move onto the next question Sorry INCORRECT answer. Nerve conduction studies can show mild axonal damage, but may fail to demonstrate any abnormality. Thermal thresholds, which are raised with small fibre damage, are usually abnormal Click here to move onto the next question Nerve conduction studies are almost always abnormal in medication related toxic neuropathy TRUE FALSE Nerve conduction studies are almost always abnormal in medication related toxic neuropathy TRUE FALSE

47. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 7 Answer the following question by clicking on either true or false. CORRECT answer. Nerve conduction studies can show mild axonal damage, but may fail to demonstrate any abnormality. Thermal thresholds, which are raised with small fibre damage, are usually abnormal Click here to move onto the next question. CORRECT answer. Nerve conduction studies can show mild axonal damage, but may fail to demonstrate any abnormality. Thermal thresholds, which are raised with small fibre damage, are usually abnormal Click here to move onto the next question. Nerve conduction studies are almost always abnormal in medication related toxic neuropathy TRUE FALSE Nerve conduction studies are almost always abnormal in medication related toxic neuropathy TRUE FALSE

48. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 8 Answer the following question by clicking on either true or false. Drug related toxic neuropathy is indistinguishable from HIV induced DSPN. TRUE FALSE Drug related toxic neuropathy is indistinguishable from HIV induced DSPN. TRUE FALSE

49. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 8 Answer the following question by clicking on either true or false. CORRECT answer. This is true both on clinical and neurophysiological grounds. The two conditions frequently co-exist. Presentation is the same as DSPN with a distal, symmetrical, predominantly lower limb, predominantly sensory, often painful, axonal neuropathy Click here to move onto the next question. CORRECT answer. This is true both on clinical and neurophysiological grounds. The two conditions frequently co-exist. Presentation is the same as DSPN with a distal, symmetrical, predominantly lower limb, predominantly sensory, often painful, axonal neuropathy Click here to move onto the next question. Drug related toxic neuropathy is indistinguishable from HIV induced DSPN. TRUE FALSE Drug related toxic neuropathy is indistinguishable from HIV induced DSPN. TRUE FALSE

50. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 8 Answer the following question by clicking on either true or false. Sorry INCORRECT answer. This is true both on clinical and neurophysiological grounds. The two conditions frequently co-exist. Presentation is the same as DSPN with a distal, symmetrical, predominantly lower limb, predominantly sensory, often painful, axonal neuropathy. Click here to move onto the next question Sorry INCORRECT answer. This is true both on clinical and neurophysiological grounds. The two conditions frequently co-exist. Presentation is the same as DSPN with a distal, symmetrical, predominantly lower limb, predominantly sensory, often painful, axonal neuropathy. Click here to move onto the next question Drug related toxic neuropathy is indistinguishable from HIV induced DSPN. TRUE FALSE Drug related toxic neuropathy is indistinguishable from HIV induced DSPN. TRUE FALSE

51. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 9 Answer the following question by clicking on either true or false. Gullian Barre syndrome is a late complication of HIV infection. TRUE FALSE Gullian Barre syndrome is a late complication of HIV infection. TRUE FALSE

52. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 9 Answer the following question by clicking on either true or false. Sorry INCORRECT answer. GBS usually occurs at primary infection or seroconversion, but is rarely associated with immune reconstitution. HIV infection should be excluded in any patient presenting with GBS as it can be clinically indistinguishable from GBS in HIV-seronegative individuals. Click here to move onto the next question Sorry INCORRECT answer. GBS usually occurs at primary infection or seroconversion, but is rarely associated with immune reconstitution. HIV infection should be excluded in any patient presenting with GBS as it can be clinically indistinguishable from GBS in HIV-seronegative individuals. Click here to move onto the next question Gullian Barre syndrome is a late complication of HIV infection TRUE FALSE Gullian Barre syndrome is a late complication of HIV infection TRUE FALSE

53. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 9 Answer the following question by clicking on either true or false. CORRECT answer. GBS usually occurs at primary infection or seroconversion, but is rarely associated with immune reconstitution. HIV infection should be excluded in any patient presenting with GBS as it can be clinically indistinguishable from GBS in HIV-seronegative individuals. Click here to move onto the next question. CORRECT answer. GBS usually occurs at primary infection or seroconversion, but is rarely associated with immune reconstitution. HIV infection should be excluded in any patient presenting with GBS as it can be clinically indistinguishable from GBS in HIV-seronegative individuals. Click here to move onto the next question. Gullian Barre syndrome is a late complication of HIV infection TRUE FALSE Gullian Barre syndrome is a late complication of HIV infection TRUE FALSE

54. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 10 Answer the following question by clicking on either true or false. HIV myelopathy typically presents with lower limb spasticity and a mid-thoracic sensory level TRUE FALSE HIV myelopathy typically presents with lower limb spasticity and a mid-thoracic sensory level TRUE FALSE

55. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 10 Answer the following question by clicking on either true or false. Sorry INCORRECT answer. Limbs may be numb or dysaesthetic, but as the damage is diffuse in HIV myelopathy, a discrete sensory level is unusual and suggests a different cause. Click here to move onto the next question Sorry INCORRECT answer. Limbs may be numb or dysaesthetic, but as the damage is diffuse in HIV myelopathy, a discrete sensory level is unusual and suggests a different cause. Click here to move onto the next question HIV myelopathy typically presents with lower limb spasticity and a mid-thoracic sensory level TRUE FALSE HIV myelopathy typically presents with lower limb spasticity and a mid-thoracic sensory level TRUE FALSE

56. HIV NEUROPATHY Learning Objectives Introduction DSPN Pathophysiology Symptoms and SignsSymptoms and Signs Diagnosis Medication related toxic neuropathyMedication related toxic neuropathy Demyelination Other Neuropathies Treatment HIV Myelopathy Key Points Summary Questions Question 10 Answer the following question by clicking on either true or false. CORRECT answer. Limbs may be numb or dysaesthetic, but as the damage is diffuse in HIV myelopathy, a discrete sensory level is unusual and suggests a different cause. Click here to finish session. CORRECT answer. Limbs may be numb or dysaesthetic, but as the damage is diffuse in HIV myelopathy, a discrete sensory level is unusual and suggests a different cause. Click here to finish session. HIV myelopathy typically presents with lower limb spasticity and a mid-thoracic sensory level TRUE FALSE HIV myelopathy typically presents with lower limb spasticity and a mid-thoracic sensory level TRUE FALSE

57. Congratulations on completing this module and thank you for using NeuroID: elearning. We hope to see you at a NeuroID: Liverpool Neurological Infectious Diseases Course soon. Download a certificateDownload a certificate and then to finish the session CLICK HERE.CLICK HERE

58. Liverpool Medical Institution, UK Provisional date: May 2013 NeuroID 2013: Liverpool Neurological Infectious Diseases Course Ever struggled with a patient with meningitis or encephalitis, and not known quite what to do? Then the Liverpool Neurological infectious Diseases Course is for you! For Trainees and Consultants in Adult and Paediatric Neurology, Infectious Diseases, Acute Medicine, Emergency Medicine and Medical Microbiology who want to update their knowledge, and improve their skills. For more information and to REGISTER NOW VISIT: www.liv.ac.uk/neuroidcoursewww.liv.ac.uk/neuroidcourse Presented by Leaders in the Field Commonly Encountered Clinical Problems Practical Management Approaches Rarities for Reference Interactive Case Presentations State of the Art Updates Pitfalls to Avoid Controversies in Neurological Infections To learn more about neurological infectious diseases… Convenors: Prof Tom Solomon, Dr Enitan Carrol, Dr Rachel Kneen, Dr Nick Beeching, Dr Benedict Michael Feedback from previous course: “Would unreservedly recommend to others” “An excellent 2 days!! The best course for a long time”