Transcript Neuro complications of HIV Powepoint Presentation

Neurological
complications of HIV
Will Chegwidden, Senior Occupational Therapist &
Emma McGettigan, Senior Physiotherapist
Infection & Immunity Speciality Group
Barts Hospital
August 2005
Outline of session
 Classification of HIV impairment and HIV
neurological impairment
 Neuropathogenesis of HIV
 CNS involvement
 PNS involvement
 Issues for therapists and discussion
Classification system

To understand how neurological impairment
occurs in HIV, it is helpful to use a classification
system of how impairment occurs generally in
HIV disease
 One way is to divide in to the following five
categories:
1. Opportunistic Infections
2. Malignancies
3. Auto-immune and reconstitution diseases
4. Constitutional disease
5. Other /multi-factorial / poorly understood
How being HIV+ leads to illness or
impairment
1. OI’s: Immunosupressed state renders individual
susceptible to infections / illnesses “opportunistic
infections” (most widely understood)
2. Autoimmune diseases and reconstitution
diseases where the immune system is
“overactive” e.g. joint disease (not fully
understood)
3. Malignancies – Some malignancies much more
prevalent with HIV – unsure why, some links to
other viruses
4. Constitutional Disease: The action of HIV at
cellular level directly causing illness
“constitutional symptoms” (not fully understood)
Disease groupings
 OIs:
– Viral Infections (CMV, HSV, PML, HPV)
– Bacterial Infections (TB, MAI, Salmonella)
– Protozoal Infections (PCP, Toxoplasmosis)
– Fungal Infections (Cryptococcyl Meningitis, Candida)
 Malignancies (KS, CNS lymphoma, Burketts, MCD)
 Autoimmune diseases (Arthraligias, GBS)
 Constitutional Conditions (HIVE/HAD/ADC, DSPN,
Wasting Syndromes)
Neuropathogenesis

1.
2.
3.
4.
5.
Neurological impairment can occur through
several routes:
As a result of opportunistic infections
As a result of HIV related malignancies
As a result of autoimmune disorders
Directly related to the action of HIV (can be
CNS or PNS related)
Multifactorial / drug related / not
understood
1. Opportunistic infections with
CNS involvement
 Cerebral toxoplasmosis
 PML
 Meningitis (Cryptococcyl meningitis, TB
meningitis)
 Encephalitis (CMV, HSV, VZV)
 Neurosyphilis
2. HIV related malignancies with
neuro involvement
 Primary lymphoma (most common)
 Kaposi’s sarcoma with cerebral involvement
(rare)
 Multiple lymphomas with either CNS
(including spinal cord compression) or rarely
PNS involvement (ie secondary CNS/PNS
lymphomas)
3. Autoimmune disorders with
neuro involvement
 Guillain-Barré Syndrome (GBS)
 Inflammatory Demyelinating Polyneuropathy
(IDP)
4. Direct action of HIV
 AIDS Dementia Complex (ADC) or HIV
Associated Dementia (HAD)
 Distal Symmetrical Polyneuropathy (DSPN)
 Mononeuritis multiplex
 Vacuolar Myolopathy
 ?Wasting Syndromes (although cardiac
system now implicated more)
5. Multifactorial / drug related /
poorly understood
 “Neuromuscular weakness syndrome”
 Role of drugs in peripheral neuropathy
Direct action of HIV in the CNS
 HIV can easily cross the blood brain barrier
 HIV thought to chiefly target phagocytic
macrophages, but also astrocytes, microglia
and monocytes
 Do not affect directly affect CNS neurons or
oligodendrocytes
Theories of how HIV crosses the
blood brain barrier
 Different theories including:
 Infected monocytes and lymphocytes traffic
across the BBB as part of their normal
immune surveillance role
 Blood brain barrier weakened by this
process – leading to increased trafficking
 Monocytes differentiate in to microglia and
macrophages
Theories of how HIV crosses the
blood brain barrier
 Also theory that meningeal macrophages
infiltrate the CNS through the CSF
compartment
 May also be a combination of these
processes
 Neurotoxic viral proteins released in to CNS
by HIV infected cells resulting in neuronal
injury / death
Direct action of HIV in the PNS
 Thought that HIV cells can lead to axonal
degeneration (resulting in DSPNs)
 Thought that HIV can lead to inflammation /
demylination (resulting in inflammatory
demyelinating neuropathies)
Principles of HIV Neurology
 Time Locking – Neurological compliocations are
directly related to the duration of HIV disease,
degree of advancement of HIV disease
 Parallel Tracking – Existence of muliple
pathologies in different parts of the nervous
system (cerebral, spinal cord, peripheral nerves)
 Layering – multiple complications in one part of
the nervous system
 Unmasking – previously compensated deficits may
be unmasked by occurrence of an additional insult
Presentations
 Vary wildly
 Often multiple pathologies on different
courses
 Often hard to diagnose, especially if already
treated empirically
 May not be HIV related!
Conditions
 Now going to present the most commonly
seen conditions at BLT
 Would be good to share all our experience
on prevalence, experience of treating and
progression of disease
 We can collate and feed back to therapists
who aren’t able to attend, especially those
outside of London
HIV and
CNS involvement
Cerebral Toxoplasmosis
 Most common CNS impairment seen in HIV
 Is a reactivation of a latent protozoal
infection
 Can also affect myocardium, lung skeletal
muscle
 Generally presents as multiple enhancing
lesions with perifocal oedema in the basal
ganglia and grey-white matter interface of
the cerebral hemispheres, although can be
in any part of brain
Toxoplasmosis
Toxoplasmosis
 Common signs and symptoms
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Headache, fever
Confusion
Lethargy
Seizure (may be initial clinical manifestation)
Focal neurologic signs (50%-60% of HIV-infected cases)
 Usually hemiparesis or visual field defects
 Treatment
– Antio-toxo drugs: Sulfadiazine, pyrimethamine,
clindamycin, pyrimethamine, folinic acid
Toxoplasmosis
 Usually responds well to treatment
 Usually the worse the initial presentation,
the longer the recovery; may have some
long term residual deficits
 Can sometimes have multiple small lesions
which present with quite specific / unusual
sensory / motor / cognitive symptoms
Toxoplasmosis
 Therapy usually “treat what you assess” –
relearning gait / UL movement through normal
movement approach; cognitive rehab; use of
functional activity etc.
 Need to be aware of visual field deficits
 Great to work with as generally will recover
 ?Impact of early intervention – usually recover
quickly at first – may be more important where
tone / positioning is an issue
PML: Progressive Multifocal
Leukoencephalopathy
 Used to be more common and was nearly always
fatal; now not seen that often
 Is a reactivation of a latent JC virus (due to
immunosuppression) – often seen more in more
severely immunocompromised people
 Appears as patchy white matter on scans, often
bilateral, asymmetrical scalloped lesions in subcortical white matter, often in parietal lobe
 Usually gradual onset
PML: Progressive Multifocal
Leukoencephalopathy
 Common presenting symptoms and signs
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–
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Hemiparesis
Gait abnormality
Speech disturbances
Cognitive dysfunction
Dysarthria
Ataxia
Sensory loss
Vertigo
Visual impairment
PML: Progressive Multifocal
Leukoencephalopathy
 No specific PML treatment; aim is to
improve immune health therefore usually
treatment is with ARVs (although cidofovir
sometimes used)
 Still often fatal; survivors tend to have
residual dysfunction in some or all of the
presenting deficit areas
PML: Progressive Multifocal
Leukoencephalopathy
 Therapy approach is again to treat what you
find – in more advanced disease may need
to look at positioning to discourage poor
movement or even prevent contracture; or
looking at managing advanced dementia /
behaviour
 If patient does survive may require some
compensation on discharge e.g.
supervision, wheelchairs etc.
Cryptococcyl meningitis, TB
meningitis
 Both quite common presentations
 Crypto caused by fungal infection
 TB may also cause focal lesions as well as
the menigitis
 Both may or may not have other systemic
illness associated e.g. Cryptococcosis, TB
lung, spine, miliary TB
Cryptococcyl meningitis, TB
meningitis
 Symptoms
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–
–
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Headache (without focal signs)
Fever
Altered mental status
Nausea and/or vomiting
May have some focal deficits, cranial nerve features
 Therapy input may be around focal deficits /
cranial nerve involvement; patients also typically
become deconditioned and lack balance as they
recover so often benefit from general functional /
activity tolerance approach
Cryptococcyl meningitis, TB
meningitis
 Crypto treated with IV amphotericin /
fluconazole
 TB treated with standard TB therapy
 Both generally respond reasonably well;
crypto quite often relapses a few times
before treated successfully
 Either sometimes may require a shunt top
effectively manage the raised ICP
CMV Encephalitis (and others)
 CMV= cytomegalovirus
 Quite common; CMV encephalitis is a
reactivation of latent CMV infection features cell death in meninges and periventricular area
 Often associated with a CMV retinitis
 Rapidly progressing; responds well to
treatment if caught in time otherwise
responds poorly
CMV Encephalitis (and others)
 Treatment is usually IV ganciclovir,
valganciclovir, foscarnet, cidofovir – these
drugs can be quite toxic
 Presentations vary, however usually involve
confusion, headache, delirium
 Can have focal neurology, cranial nerve
deficits
CMV Encephalitis (and others)
 Therapy approach again is treat what
presents; often complicated by permanent
visual field loss
 Other encephalitis presentations include
HSV (Herpes Simplex Virus) and VZV
(Varicellar Zoster Virus)
Primary CNS Lymphoma
 1000-4000 times more common in HIV+
population than in immunocompetent
population
 Doesn’t correlate with low CD4 counts
 Pathogenesis not fully understood but
known to be linked to the Epstein-Barr Virus
 Thought that long term low level immune
system damage may be contributing factor
Primary CNS Lymphoma
 Is generally non-Hodgkin’s B-cell type with high
mitotic rate; tumours usually double in size in 14
days. (can also be a Burkitt or more rarely a
Primary Effusion Lymphoma)
 Can be multifocal (50%) and appear in uncommon
locations with greater frequency than in non-HIV
population
 Studies have average survival rates from
diagnosis between 3 and 24 months
 May be treated actively or palliatively with
radiotherapy (usually palliative) or high dose
methotrexate (chemo)
Primary CNS Lymphoma
 Disagreement between researchers whether
discontinuing or continuing ARVs throughout
treatment is most beneficial
 Therapy input is usually initially around
advice / treatment to help maintain function /
independence and planning for deterioration
/ palliative approach
HIV Encephalopathy
HIVE / ADC / HAD
 Number of terms used overlappingly to
describe poorly understood syndromes of
long term infiltration of HIV into the CNS
 Names include:
– HIV-1-associated dementia complex (HAD)
– AIDS Dementia Complex (ADC)
– HIV encephalitis / HIV Encephalopathy (HIVE)
– multinucleated giant-cell encephalitis
HIV Encephalopathy
HIVE / ADC / HAD
 Can be seen in early disease but more common later
 Severe form less common since the introduction of
HAART
 Many long term diagnosed however do report mild
cognitive problems e.g. memory problems, and show
some general brain atrophy on scans
 On scans often higher concentrations changes in the
basal ganglia - ?due to numbers of microglia in the
brain – thought to be why high rates of extra-pyramidal
signs / symptoms seen
HIV Encephalopathy
HIVE / ADC / HAD
 Symptoms generally develop over weeks to
months in the following domains:
 Cognition
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Decreased concentration
Forgetfulness, particularly daily or recent events
Slowing of thought processes
Global dementia
Psychomotor slowing: verbal responses delayed, near
or absolute mutism, vacant stare
– Unawareness of illness, disinhibition
– Confusion, disorientation
– Organic psychosis
 Motor function
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Unsteady gait
Clumsiness
Tremor
Leg weakness (legs more than arms)
Loss of coordination, impaired handwriting
 Behaviour
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Social withdrawal
Apathy
Personality change
Agitation
Hallucinations
 Other
– Headaches
– Generalized seizures
– Ataxia
HIV Encephalopathy
HIVE / ADC / HAD
 Treatment is via reducing viral load and viral
activity in the CNS, therefore treatment is
primarily HAART
 Need to consider ARVs with best CNS
penetration e.g. zidovudine (AZT), abacavir,
nevirapine
 Difficult to measure drug levels as not
known whether CSF drug levels always
correlate with cerebral levels; (not practical
to brain biopsy!)
HIV Encephalopathy
HIVE / ADC / HAD
 Therapy input more akin to treating
someone with dementia; early treatment
may be looking at memory strategies; later
stages may require behavioural
management and reality orientation /
validation
 Severe HIVE may require 24 hour
supervision
Vacuolar Myopathy
 “Holes” in spinal cord
 Clinical Features – onset over weeks-months of:
– Bilateral lower extremity stiffness and weakness with variable
sensory disturbances
– Gait unsteadiness
– Bladder and erectile dysfunction
– Hyperreflexia and Babinski signs
– Spastic paraparesis with no definite sensory involvement
– Loss of proprioception and vibration sense
 Thought to be secondary to overactive immune system
producing excessive cytokines, or some poorly understood
metabolic imbalance; may be related to HTLV-I and HTLV-II
HIV and PNS Involvement
DSPN: Distal Symmetrical
Sensory Polyneuropathy
 Occurs in many HIV+ patients with varying
severity
 Poorly understood aetiology but could be
related to malnutrition and resultant wasting
of peripheral nerves, or could be neurotoxic
effect of cytokines
 Can also be secondary to NRTI use e.g.
AZT
DSPN
 Often occurs in a glove and stocking distribution
but there is great variance in self report
 Can range from mild parasthesia / numbness /
pins and needles through to severe
hypersensitivities, or dysesthesias (burning,
stabbing pain)
 Can lead to poor upper limb coordination or mildly
impaired mobility / clumsiness, attributable to
reduced sensory feedback
DSPN
 Can progress to actual muscle weakness,
particularly foot intrinsics (result of long term
de-inervation)
 Sometimes use EMG studies to diagnose
 Often treated with quite high dose
analgesics which can interact with other
medications or have lifestyle implications
 Can be very disabling
DSPN
 Therapy input can be looking at
– Psychogenic management of pain e.g.
relaxation
– Task planning – how to avoid parts of tasks that
elicit pain
– Safety aspects e.g. temperature sensation,
retraining to be aware of feet catching on stairs
– Padded / built up equipment to reduce / alter
sensory input to help mange pain, or provide
more gross proprioceptive feedback
Inflammatory Demyelinating
Polyneuropathy (IDP)
 IDP, and it’s more severe cousin GullainBarre Syndrome sometimes occur acutely in
otherwise well HIV+ patients, or in HIV+
patients with advanced disease.
 Seems to be some sort of auto-immune
response that attacks the myelins sheath –
mechanism is poorly understood
 Treated with IVIg
(Ascending) Neuromuscular
Weakness Syndrome
 Presents as rapidly progressing
sensorimotor neuropathy, can lead to
respiratory failure
 Thought to be related to NRTI use
Mononeuritis Multiplex
 Can present as multifocal sensory and/or
motor abnormalities and is due to
asymmetrical involvement of individual
peripheral and cranial nerves; may be a
mixed neuropathy (motor, sensory,
autonomic)
 Thought to be diectly related to action of HIV
 Poorly understood
Issues for therapists
Deciding on treatment approaches
and techniques
 Not knowing what you are treating
 Unsure prognoses
 Multiple pathologies in one patient with
differing courses
 Rehab versus compensation
 Evidence base
 Consent for treatment
 Flexibility
Related issues that impact
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Stigma and confidentiality
Impact of asylum and immigration
Co-morbid drug use and other social issues
Referring on to other facilities
Placing young physically or cognitively
impaired adults ?care in the community
 Infection control
Solutions existing
 Strong MDT
 Therapists input to diagnosis vital
 Close working with partner agencies, e.g.
community neurorehab teams, Queen’s Square,
RNRU’s
 HRBI Unit at Mildmay
 PT and OT HIV special interest groups
 Huge research opportunities
 Working with African and emerging populations
 The internet
Brainstorm time
 What other experiences have people to
share?
 What are the biggest challenges?
 What ideas for inpatient rehabilitation
facilities and community rehabilitation do
people have?
 Would people be interested in research?
References / resources
 The National AIDS Manual – information on
presentations, illnesses and treatments
 www.hivinsite.com
 www.clinicaloptions.com
 www.nam.org.uk
 www.i-base.org.uk
 www.avert.org.uk
 www.unaids.com