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Neurological complications of HIV

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Neurological complications of HIV Will Chegwidden, Senior Occupational Therapist & Emma McGettigan, Senior Physiotherapist Infection & Immunity Speciality Group – PowerPoint PPT presentation

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Title: Neurological complications of HIV


1
Neurological complications of HIV
  • Will Chegwidden, Senior Occupational Therapist
    Emma McGettigan, Senior Physiotherapist
  • Infection Immunity Speciality Group
  • Barts Hospital
  • August 2005

2
Outline of session
  • Classification of HIV impairment and HIV
    neurological impairment
  • Neuropathogenesis of HIV
  • CNS involvement
  • PNS involvement
  • Issues for therapists and discussion

3
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
  • Opportunistic Infections
  • Malignancies
  • Auto-immune and reconstitution diseases
  • Constitutional disease
  • Other /multi-factorial / poorly understood

4
How being HIV leads to illness or impairment
  • OIs Immunosupressed state renders individual
    susceptible to infections / illnesses
    opportunistic infections (most widely
    understood)
  • Autoimmune diseases and reconstitution diseases
    where the immune system is overactive e.g.
    joint disease (not fully understood)
  • Malignancies Some malignancies much more
    prevalent with HIV unsure why, some links to
    other viruses
  • Constitutional Disease The action of HIV at
    cellular level directly causing illness
    constitutional symptoms (not fully understood)

5
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)

6
Neuropathogenesis
  • 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

7
Opportunistic infections with CNS involvement
  • Cerebral toxoplasmosis
  • PML
  • Meningitis (Cryptococcyl meningitis, TB
    meningitis)
  • Encephalitis (CMV, HSV, VZV)
  • Neurosyphilis

8
2. HIV related malignancies withneuro involvement
  • Primary lymphoma (most common)
  • Kaposis sarcoma with cerebral involvement (rare)
  • Multiple lymphomas with either CNS (including
    spinal cord compression) or rarely PNS
    involvement (ie secondary CNS/PNS lymphomas)

9
3. Autoimmune disorders withneuro involvement
  • Guillain-Barré Syndrome (GBS)
  • Inflammatory Demyelinating Polyneuropathy (IDP)

10
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)

11
5. Multifactorial / drug related / poorly
understood
  • Neuromuscular weakness syndrome
  • Role of drugs in peripheral neuropathy

12
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

13
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

14
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

15
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)

16
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

17
Presentations
  • Vary wildly
  • Often multiple pathologies on different courses
  • Often hard to diagnose, especially if already
    treated empirically
  • May not be HIV related!

18
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
    arent able to attend, especially those outside
    of London

19
HIV and CNS involvement
20
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

21
Toxoplasmosis
22
Toxoplasmosis
  • Common signs and symptoms
  • 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

23
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

24
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

25
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
    sub-cortical white matter, often in parietal lobe
  • Usually gradual onset

26
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27
PML Progressive Multifocal Leukoencephalopathy
  • Common presenting symptoms and signs
  • Hemiparesis
  • Gait abnormality
  • Speech disturbances
  • Cognitive dysfunction
  • Dysarthria
  • Ataxia
  • Sensory loss
  • Vertigo
  • Visual impairment

28
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

29
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.

30
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

31
Cryptococcyl meningitis, TB meningitis
  • Symptoms
  • 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

32
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

33
CMV Encephalitis (and others)
  • CMV cytomegalovirus
  • Quite common CMV encephalitis is a reactivation
    of latent CMV infection - features cell death in
    meninges and peri-ventricular area
  • Often associated with a CMV retinitis
  • Rapidly progressing responds well to treatment
    if caught in time otherwise responds poorly

34
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

35
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)

36
Primary CNS Lymphoma
  • 1000-4000 times more common in HIV population
    than in immunocompetent population
  • Doesnt 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

37
Primary CNS Lymphoma
  • Is generally non-Hodgkins 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)

38
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

39
HIV EncephalopathyHIVE / 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

40
HIV EncephalopathyHIVE / 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

41
HIV EncephalopathyHIVE / ADC / HAD
  • Symptoms generally develop over weeks to months
    in the following domains
  • Cognition
  • 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

42
  • Motor function
  • Unsteady gait
  • Clumsiness
  • Tremor
  • Leg weakness (legs more than arms)
  • Loss of coordination, impaired handwriting
  • Behaviour
  • Social withdrawal
  • Apathy
  • Personality change
  • Agitation
  • Hallucinations
  • Other
  • Headaches
  • Generalized seizures
  • Ataxia

43
HIV EncephalopathyHIVE / 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!)

44
HIV EncephalopathyHIVE / 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

45
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

46
HIV and PNS Involvement
47
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

48
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

49
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

50
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

51
Inflammatory Demyelinating Polyneuropathy (IDP)
  • IDP, and its more severe cousin Gullain- Barre
    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

52
(Ascending) Neuromuscular Weakness Syndrome
  • Presents as rapidly progressing sensorimotor
    neuropathy, can lead to respiratory failure
  • Thought to be related to NRTI use

53
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

54
Issues for therapists
55
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

56
Related issues that impact
  • 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

57
Solutions existing
  • Strong MDT
  • Therapists input to diagnosis vital
  • Close working with partner agencies, e.g.
    community neurorehab teams, Queens Square,
    RNRUs
  • HRBI Unit at Mildmay
  • PT and OT HIV special interest groups
  • Huge research opportunities
  • Working with African and emerging populations
  • The internet

58
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?

59
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
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