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

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

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

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 Categories France India Braz Number of patients 148 67 230 Period 1982 -88 1988 -96 1985 Focal disorders • Cerebral toxoplasmosis 44% 16% 34% • Primary lymphoma 11% 0 4% • PML 3% 0 0 Non-focal disorders • CMV encephalitis 17% 9% 7. 9%

CNS complications of HIV Necropsy series Categories France Number of patients Period Meningitis • Cryptococcal meningitis • Tuberculosis • Aseptic meningitis • Bacterial meningitis India Braz 148 1982 -88 67 1988 -96 230 1985 1% 0. 6% NA NA 10% 15% NA NA 13. 5 0 NA NA

CNS complications of HIV Clinical series Categories Cote d’ Ivoire Mexico Number of patients 42 40 130 Period 1995 1986 -88 1986 Focal disorders • Cerebral toxoplasmosis 36% 7. 5% 4. 6% • Primary lymphoma 0 2. 5% 8. 4% • PML 0 2. 5% 3. 8% Non-focal disorders • CMV encephalitis 0 0 18. 5%

CNS complications of HIV Clinical series Categories Cote d’ Ivoire Number of patients Period Meningitis • Cryptococcal meningitis • Tuberculosis • Aseptic meningitis • Bacterial meningitis Mexico 42 1995 40 1986 -88 130 1986 12% 7% 0 12% 17. 5% 10% 7. 5% 0 1% 6. 1% 0

Prevalence of AIDS defining illness in Thailand 1987 -1996 AIDS defining illness Chiengmai Bamras Ram 1987 -1992 1990 -1994 19 n = 307 n = 241 n= Tuberculosis 31. 3 Cryptococcosis Pneumocystis carinei 50. 2 24. 1 13. 4 40. 9 33 17. 0 23. 3 16. 6 14. 3 Toxoplasmosis 7. 5 1. 6 6. 2 Penicilliosis marneffei 16. 0 3. 7 1. 9 3

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 Death Loss FU at day 28 Sign out at day 8 Survive (day 70) 23 4(day 1, 3, 19, 21( 1 1 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: 668 -72. 2205 patients with cultured proved Tbc 10% 2% 450 HIV 1750 Non-HIV

Tuberculous meningitis in HIV Berenguer J, Moreno S, Laguna F, et al. N Eng J Med 1992; 326: 668 -72. • 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 CD 4 (<200) were associated with reduced survival

Management of focal brain lesions in HIV-infected patients COST BENEFIT

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

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 % • • • 96 84 48 44. 4 Headache Fever Stiff neck Hemiparesis Conscious change – Drowsy – Stupor • Cranial nerve palsy • Seizure 42. 91 3. 85 42. 31 39

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds % • Number of lesions 1 36 2 18 3 18 4 or more 34

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds % • Location Basal ganglia 60 Frontal 40 Parietal 40 Occipital 21 Temporal 12 Mid brain 4

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds % • Density Isodensity 77 Hypodensity 26 Hyperdensity 0 Calcification 0

CT findings of CNS toxoplasmosis in AIDS at Chiang Mai hospital CT findinds % • Enhancement Irregular ring 67 Nodular 44 Gyral 8 • Edema Mild 17 Moderate 83

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 contrast April 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 immunesuppression • 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