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

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 toxicityDrug toxicityDrug 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 HIVNecropsy series

Categories France India Brazil

Number of patients 148 67 230Period 1982-88 1988-96 1985-90Focal disorders•Cerebral toxoplasmosis 44% 16% 34%•Primary lymphoma 11% 0 4%•PML 3% 0 0Non-focal disorders•CMV encephalitis 17% 9% 7.9%

CNS complications of HIVNecropsy series

Categories France India Brazil

Number of patients 148 67 230Period 1982-88 1988-96 1985-90Meningitis•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 130Period 1995 1986-88 1986-88Focal 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 130Period 1995 1986-88 1986-88Meningitis•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 Siriraj1987-1992 1987-1992 1990-1994 1993-1996n = 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%

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 HIVBerenguer J, Moreno S, Laguna F, et al. N Eng J Med 1992;326:668-72.

2205 patientswith cultured proved Tbc

Meningitis

Not meningitis

450 HIV

10%

1750 Non-HIV

2%

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

BENEFITCOST

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 settingReal 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 %

• 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 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 polyradiculopathyLumbrosacral 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