Neurological Complications of AIDS Supoch Tunlayadechanont Ramathibodi Hospital

Neurological Complications of AIDS Common –Pathological findings (>90%) –Clinically significant problems (40-70%) Affecting all parts of the nervous system Multiple pathological processes Common neurological condition in non-HIV patients can also be found in HIV patients

Neurological Complications of AIDS Pathological processes Primary result of HIV Secondary neurologic complications Immunological complications

Neurological Complications of AIDS Time Primary result of HIV Immuno-suppression Acute viral illness Aseptic meningitis Encephalitis Asymptomatic Chronic meningitis Minor Cognitive/motor ADC Vacuolar myelopathy Distal symmetrical polyneuropathy

Neurological Complications of AIDS Time Secondary neurologic complications Immuno-suppression Opportunistic infections Neoplasms Vascular disease Nutritional and metabolic disorders Drug toxicity

Neurological Complications of AIDS Time Immunological complications Immuno-suppression CIDP Myopathy Mononeuropathy AIDP

HIV infections of the CNS in tropical areas Most (89%) of the 30.6 million of HIV infected people are estimated to live in sub-Saharan Africa and developing countries of Asia, but.. The neurological complications have been well described in other populations. Joint UNAIDS and WHO. Global AIDS surveillance. Weekly Epidemiological Record 1997;72:357-60

HIV infections of the CNS in tropical areas Local geographical, socioeconomic and variation in risks factor and prevalence of infective agents Many of the patients may be dies before some complications can develop Opportunistic infections..namely cryptococccal meningitis, toxoplasmosis and tuberculosis cause most of the morbidity and mortility

CNS complications of HIV Necropsy series CategoriesFranceIndiaBrazil Number of patients Period Focal disorders Cerebral toxoplasmosis44%16%34% Primary lymphoma11%04% PML3%00 Non-focal disorders CMV encephalitis17%9%7.9%

CNS complications of HIV Necropsy series CategoriesFranceIndiaBrazil Number of patients Period Meningitis Cryptococcalmeningitis1%10%13.5% Tuberculosis0.6%15%0 Aseptic meningitisNANANA Bacterial meningitisNANANA

CNS complications of HIV Clinical series CategoriesCote d ’ IvoireMexicoUSA Number of patients Period Focal disorders Cerebral toxoplasmosis36%7.5%4.6% Primary lymphoma02.5%8.4% PML02.5%3.8% Non-focal disorders CMV encephalitis0018.5%

CNS complications of HIV Clinical series CategoriesCote d ’ IvoireMexicoUSA Number of patients Period Meningitis Cryptococcalmeningitis12%17.5%13% Tuberculosis7%10%1% Aseptic meningitis07.5%6.1% Bacterial meningitis12%00

Prevalence of AIDS defining illness in Thailand AIDS defining illnessChiengmaiBamrasRama Siriraj n = 307n = 241 n = 235 n = 817 Tuberculosis Cryptococcosis Pneumocystis carinei Toxoplasmosis Penicilliosis marneffei

Some common (treatable) neurological complications Cryptococcal meningitis Tubercolous meningitis Toxoplasmic encephalitis Neuromuscular complications Myelopathy

Cryptococcal meningitis in patients with non- HIV and HIV infection A 10 fold increase in annual hospital admission of CM, which occurred exclusively in HIV. Duration of illness before diagnosis is shorter. Clinical presentation may be nonspecific. Heavier fungal load but less inflammatory response High intracranial pressure is still a major problem

Cryptococcal meningitis in patients with non- HIV and HIV infection A 10 fold increase in annual hospital admission of CM, which occurred exclusively in HIV. Duration of illness before diagnosis is shorter. Clinical presentation may be nonspecific. Heavier fungal load but less inflammatory response High intracranial pressure is still a major problem Immediate mortality was much higher at 60% and 30% of the patients was still alive at the end of 1 year

Treatment of CM in HIV Total 23 Death4(day 1,3,19,21) Loss FU at day 281 Sign out at day81 Survive (day 70)74-83%

Connect to sterile bags

Clinical study : Tuberculous meningitis in HIV Problem with diagnosis Culture is insensitive Anti-tuberculosis treatment can effect others

Tuberculous meningitis in HIV Berenguer J, Moreno S, Laguna F, et al. N Eng J Med 1992;326: patients with cultured proved Tbc 450 HIV 10% 1750 Non-HIV 2%

Tuberculous meningitis in HIV Berenguer J, Moreno S, Laguna F, et al. N Eng J Med 1992;326: CNS involvement in patients with tuberculosis was more common in HIV. Clinical manifestations of TBM are not different from non-HIV (adenopathy is more common in HIV) TBM can developed in HIV receiving anti-Tbc. Prolong illness before Rx (14 d ) and low CD4 (<200) were associated with reduced survival

Management of focal brain lesions in HIV-infected patients COSTBENEFIT

COST Management of focal brain lesions in HIV-infected patients Complications Occupational hazards Change in therapy Survival Local data New technology Potent antiretroviral treatment Real situation in the hospital setting

Toxoplasmic encephalitis Most common cause of focal brain lesion in AIDS Morbidity associated with brain biopsy Reluctant of neurosurgeon to perform operation Limitation of immunological and imaging diagnosis Predictable clinical and clinical response

Toxoplasmic encephalitis The diagnosis of cerebral toxoplasmosis in tropical countries should be made on clinical grounds, including the response to treatment …... …….as usually patients respond within a few days of starting therapy.

Clinical manifestations of CNS toxoplasmosis in 166 AIDS patients Chiang Mai Hosp (1990-1) Clinical manifestation% Headache96 Fever84 Stiff neck48 Hemiparesis44.4 Conscious change –Drowsy42.91 –Stupor3.85 Cranial nerve palsy42.31 Seizure39

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds% Number of lesions or more34

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds% Location Basal ganglia60 Frontal40 Parietal40 Occipital21 Temporal12 Mid brain4

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds% Density Isodensity77 Hypodensity26 Hyperdensity0 Calcification0

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds% Enhancement Irregular ring67 Nodular44 Gyral8 Edema Mild17 Moderate83

Time to Neurologic Response in 35 Patients study Luft B J, Hafner R, Korzun AH, et al. NEJM 1993;329:

Time course of response to therapy Porter SB, Sande MA. NEJM 1992;327: CLINICAL RADIOLOGICAL

March 5 with contrastApril 10 non-contrast

Neuromuscular complications Neuropathy and myopathy are often masked by other neurological or systemic conditions. Different forms of of neuropathy can be distinguished by signs and symptoms at different stage of HIV infection. Variety of pathogenesis can be involved (HIV, toxic, immune, opportunistic infections)

Distal Symmetric Polyneuropathy Usually occurs in late stages Clinical features –Distribution –Pain, paresthesia –Normal strength –Decrease ankle jerk R/O drugs Symptomatic Rx

Inflammatory demyelinating polyneuropathy Occurs at any stages Clinical features –Bilat facial weakness –Ascending weakness –Generalized areflexia –Mild sensory invlovement Electro-physio and CSF exam Immunotherapy

Progressive polyradiculopathy Lumbrosacral radiculomyelitis Occurs at late stage Clinical features –Radiating pain in cauda equina distribution –Mild sensory loss (perianal) –Sphincter dysfunction CSF examination and MRI CMV related

Mononeuritis multiplex Occurs at any stages Clinical features –Cranial nerves –Multiple peripheral nerves Pathogenesis and treatment related to stage of immune- suppression Entrapment neuropathy?

Spinal cord syndrome Vacuolar myelopathy - 1/3 (20-55%) in autopsy series - Clinical manifestation is much smaller

Vacuolar myelopathy Clinical and diagnosis Usually late HIV Develops slowly (months) Coexisting neuropathy Sensory symptoms –Loss viration and joint position sensation with relatiively preserve pain sensation. –No discrete sensory level No back pain