Transcript Neurological Complications of AIDS

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
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
Brazil
Number of patients
Period
Focal disorders
•Cerebral toxoplasmosis
•Primary lymphoma
•PML
Non-focal disorders
•CMV encephalitis
148
1982-88
67
1988-96
230
1985-90
44%
11%
3%
16%
0
0
34%
4%
0
17%
9%
7.9%
CNS complications of HIV
Necropsy series
Categories
France
India
Brazil
Number of patients
Period
Meningitis
•Cryptococcal meningitis
•Tuberculosis
•Aseptic meningitis
•Bacterial meningitis
148
1982-88
67
1988-96
230
1985-90
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
USA
Number of patients
Period
Focal disorders
•Cerebral toxoplasmosis
•Primary lymphoma
•PML
Non-focal disorders
•CMV encephalitis
42
1995
40
1986-88
130
1986-88
36%
0
0
7.5%
2.5%
2.5%
4.6%
8.4%
3.8%
0
0
18.5%
CNS complications of HIV
Clinical series
Categories
Cote d’ Ivoire Mexico
USA
Number of patients
Period
Meningitis
•Cryptococcal meningitis
•Tuberculosis
•Aseptic meningitis
•Bacterial meningitis
42
1995
40
1986-88
130
1986-88
12%
7%
0
12%
17.5%
10%
7.5%
0
13%
1%
6.1%
0
Prevalence of AIDS defining illness in Thailand
1987-1996
AIDS defining illness
Chiengmai
1987-1992
n = 307
Bamras
1987-1992
n = 241
Rama
Siriraj
1990-1994 1993-1996
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
1.6
6.2
3.5
3.7
1.9
1.7
7.5
Penicilliosis marneffei 16.0
Some common (treatable)
neurological complications
•
•
•
•
•
Cryptococcal meningitis
Tubercolous meningitis
Toxoplasmic encephalitis
Neuromuscular complications
Myelopathy
Cryptococcal meningitis in patients with nonHIV 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 nonHIV 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 day8
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.
Meningitis
2205 patients
with cultured proved Tbc
10%
Not meningitis
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 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
•
•
•
•
84
48
44.4
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