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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.
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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 AIDSPathological processes Primary result of HIV Secondary neurologic complications Immunological complications
Immuno-suppression Neurological Complications of AIDS Primary result of HIV Acute viral illness Asymptomatic ADC Aseptic meningitis Chronic meningitis Encephalitis Minor Cognitive/motor Vacuolar myelopathy Distal symmetrical polyneuropathy Time
Drug toxicity Drug toxicity Drug toxicity Immuno-suppression Neurological Complications of AIDS Secondary neurologic complications Opportunistic infections Neoplasms Vascular disease Nutritional and metabolic disorders Time
Immuno-suppression Neurological Complications of AIDS Immunological complications AIDP CIDP Mononeuropathy Myopathy Time
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 HIVNecropsy series • Categories France India Brazil • Number of patients 148 67 230 • Period 1982-88 1988-96 1985-90 • 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 HIVNecropsy series • Categories France India Brazil • Number of patients 148 67 230 • Period 1982-88 1988-96 1985-90 • Meningitis • Cryptococcal meningitis 1% 10% 13.5% • Tuberculosis 0.6% 15% 0 • Aseptic meningitis NA NA NA • Bacterial meningitis NA NA NA
CNS complications of HIVClinical series • Categories Cote d’ Ivoire Mexico USA • Number of patients 42 40 130 • Period 1995 1986-88 1986-88 • 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 HIVClinical series • Categories Cote d’ Ivoire Mexico USA • Number of patients 42 40 130 • Period 1995 1986-88 1986-88 • Meningitis • Cryptococcal meningitis 12% 17.5% 13% • Tuberculosis 7% 10% 1% • Aseptic meningitis 0 7.5% 6.1% • Bacterial meningitis 12% 0 0
Prevalence of AIDS defining illness in Thailand1987-1996 AIDS defining illness Chiengmai Bamras Rama Siriraj 1987-1992 1987-1992 1990-1994 1993-1996 n = 307 n = 241 n = 235 n = 817 Tuberculosis 31.3 50.2 40.9 33 Cryptococcosis 24.1 17.0 23.3 26 Pneumocystis carinei 13.4 16.6 14.3 26 Toxoplasmosis 7.5 1.6 6.2 3.5 Penicilliosis marneffei 16.0 3.7 1.9 1.7
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 • Death 4(day 1,3,19,21) • Loss FU at day 28 1 • Sign out at day8 1 • Survive (day 70) 74-83%
Clinical study : Tuberculous meningitis in HIV Problem with diagnosis • Culture is insensitive • Anti-tuberculosis treatment can effect others
10% 2% 450 HIV 1750 Non-HIV Tuberculous meningitis in HIVBerenguer J, Moreno S, Laguna F, et al. N Eng J Med 1992;326:668-72. 2205 patients with cultured proved Tbc
Tuberculous meningitis in HIVBerenguer 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 CD4 (<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 % • Headache 96 • Fever 84 • Stiff neck 48 • Hemiparesis 44.4 • Conscious change • Drowsy 42.91 • Stupor 3.85 • Cranial nerve palsy 42.31 • Seizure 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 studyLuft B J, Hafner R, Korzun AH, et al. NEJM 1993;329:
Time course of response to therapyPorter 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 immune-suppression • Entrapment neuropathy?
Spinal cord syndrome • Vacuolar myelopathy - 1/3 (20-55%) in autopsy series - Clinical manifestation is much smaller
Vacuolar myelopathyClinical 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