See also Overview of Delirium and Dementia and Dementia. Dementia is chronic, global, usually irreversible deterioration of cognition. Unlike almost all other forms of dementia, it tends to occur in younger people. Dementia should not be confused with delirium , although cognition is disordered in both. The following helps distinguish them:.
This conclusion seems reasonable even if not directly proven or supported by controlled observations. Timed activities are further slowed and attempts to draw complex objects may produce only simplified representations. Pathogenic cytokine activation and Hiv dementia progressive neuropathologic sequelae can be considered as immunopathologic reactions that link infection to Hiv dementia progressive. Cognitive impairments associated with HIV occur in the domains of attention, memory, verbal fluency, and visuospatial construction. What are the symptoms of HIV-associated dementia? Diagnostic Studies Clinical laboratory studies reveal the characteristic abnormalities noted commonly in ADC and, perhaps even more importantly, detect other conditions in the differential diagnosis. From Wikipedia, Hardcore series bathroom free encyclopedia. The ocular symptoms during a cholinergic crisis can mimic the symptoms of myasthenia gravis and can result when the dose of an anticholinergic drug peogressive too high.
Their cherries virginity giving birth. Information
The essential features of ADC are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Everall; S. Namespaces Article Talk. Views Read Edit View history. The History of HIV. The infected macrophages and microglia also appear to produce additional factors such as chemokines and cytokines that can affect neurons as well as other brain cells known as astrocytes. It is one cause of dementia in people infected Hiv dementia progressive HIV. Add to Any Platform. Ten out of eleven patients were on antiretroviral medication and none scored within the demented range on the Hiv dementia progressive Dementia Progreseive. Histopathologicallyit is identified by the infiltration of monocytes and macrophages into the central nervous system CNSgliosispallor of myelin sheathsabnormalities of dendritic processes and neuronal loss. In addition to a complete medical history Hig extensive neurological motor and sensory exam, diagnostic procedures for dementia may include the following: Mental status test. Neuropsychological testing. Writing lists can help you stay organized and demejtia important details. Continue Reading.
HAND may include neurological disorders of various severity.
- HAND may include neurological disorders of various severity.
- See also Overview of Delirium and Dementia and Dementia.
- Most people don't know that the HIV infection actually makes its way to the brain early in the disease process.
- It is a condition classified by the Centers for Disease Control and Prevention CDC as an AIDS-defining condition and is characterized by the deterioration of cognitive, motor and behavioral function, the symptoms of which can include:.
The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations. In this review, we will describe the history of HIV-associated neurocognitive disorders HAND , an umbrella term that includes memory, processing speed, and concentration and attentional deficits in individuals living with HIV , important terminology and classification systems used to diagnose HIV-associated neurocognitive disorders, and the clinical manifestations and management of HIV-associated neurocognitive disorders.
This, in combination with the compound effects of age-related cognitive changes in individuals affected by HIV, has resulted in an increasing prevalence of cognitive impairment in individuals living with HIV. These categories have important prognostic implications.
Prior to antiretroviral therapy s. After discovery of and increased accessibility to antiretroviral therapy and beyond. With the introduction of highly active antiretroviral therapy the incidence of HIV-associated dementia, the most severe form of HIV-associated neurocognitive disorders, has decreased but the absolute prevalence of HIV-associated neurocognitive disorder has increased every decade given the longer life expectancy of individuals with HIV on combination antiretroviral therapy.
In , Antinori and colleagues developed classification criteria to standardize nomenclature surrounding neurocognitive diagnosis in persons living with HIV PLWH.
The Frascati criteria consist of 3 separate clinical entities Antinori et al and are detailed in Table 1. Asymptomatic neurocognitive impairment includes individuals with cognitive performance 1 standard deviation below the mean in 2 or more cognitive domains without documented impairment in activities of daily living.
Mild neurocognitive disorder includes individuals with cognitive performance 1 standard deviation below the mean in 2 or more cognitive domains with mild documented difficulties in activities of daily living. HIV-associated dementia includes those with cognitive performance falling 2 standard deviations below the mean in 2 or more domains and severe difficulties in performance of activities of daily living.
Other confounding factors or non-HIV related diagnoses must be excluded in order to attribute cognitive impairment to the underlying HIV infection. These alternative diagnoses may include substance abuse, other causes of dementia, or pseudo-dementia associated with an underlying psychiatric condition.
A key point of differentiation is between asymptomatic neurocognitive impairment and symptomatic disorders mild neurocognitive disorder and HIV-associated dementia , which differ based on impairment in activities of daily living.
Table 1. Since the advent of antiretroviral therapy, most patients present with mild forms of HIV-associated neurocognitive disorder resulting in a shift from severe to milder HIV-associated neurocognitive disorder subtypes in the posttreatment era Sacktor et al Milder forms of HIV-associated neurocognitive disorder have important prognostic implications, as individuals with asymptomatic neurocognitive impairment have an increased risk of meeting criteria for symptomatic impairment mild neurocognitive disorder and HIV-associated dementia over the next few years Grant et al Although only a small subset of patients may progress to frank dementia, even patients with the mildest of symptoms can have their quality of life affected by disruption in their ability to perform activities of daily living and, importantly, in their adherence to medication McArthur The term "HIV encephalitis" should be reserved for the pathological features of multinucleated giant cell encephalitis with HIV identified in the brain and not used to describe the clinical syndrome.
Similarly, although HIV-associated dementia can develop concurrently with other HIV-associated neurologic disorders, such as myelopathy and neuropathy, these diseases are discrete clinical entities separate from HAND with distinct manifestations, courses, and pathogenic mechanisms.
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Home Contents. Patel of Yale University has no relevant financial relationships to disclose. Originally released April 1, ; last updated August 21, ; expires August 21, In This Article Introduction. All rights reserved. For Faculty OSS.
Living with HIV-associated dementia? In patients who have HIV infection but not dementia, these values help determine how likely HIV-associated dementia is to develop. Examination and evaluation are essential in determining the presence and extent of the dementia. Stage 4: Near vegetative state. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors.
Hiv dementia progressive. What causes HIV-associated dementia?
Dementia only exists when neurocognitive impairment in the patient is severe enough to interfere markedly with day-to-day function. That is, the patient is typically unable to work and may not be able to take care of him or herself. Before this, the patient is said to have a mild neurocognitive disorder. While the progression of dysfunction is variable, it is regarded as a serious complication and untreated can progress to a fatal outcome.
Diagnosis is made by neurologists who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scans MRI or CT scan and a lumbar puncture to evaluate the cerebrospinal fluid.
No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings and examination can reliably establish the diagnosis when performed by experienced clinicians. The amount of virus in the brain does not correlate well with the degree of dementia , suggesting that secondary mechanisms are also important in the manifestation of ADC.
However, the cause of ADC can be difficult to discern because the central nervous system can be damaged by a number of other causes related to HIV infection:. Many researchers believe that HIV damages the vital brain cells, neurons , indirectly.
According to one theory, HIV either infects or activates cells that protect the brain, known as macrophages and microglia. These cells then produce toxins that can set off a series of reactions that instruct neurons to kill themselves.
The infected macrophages and microglia also appear to produce additional factors such as chemokines and cytokines that can affect neurons as well as other brain cells known as astrocytes. The affected astrocytes, which normally nurture and protect neurons, also may now end up harming neurons. Tat is secreted and induces reactivity in astrocytes through increased GFAP expression. HIV enters the brain early on in the infection.
Normally, the blood—brain barrier BBB serves as a protective mechanism by preventing entry of foreign substances; disruption of the BBB by HIV contributes to the progression of infection. When infected, immune cells are able to better migrate into tissues compared to uninfected cells.
Infected microglia add to the production of the virus. This activation of the microglia may contribute to the process of neuropathogenesis that spreads the infection to nearby cells. The toxicity spreads through a gap junction-dependent mechanism. HIV is associated with pathological changes in mainly subcortical and fronto-striatal areas of the brain, including the basal ganglia , deep white matter, and hippocampal regions.
Neuroimaging studies of HIV patients indicate that significant volume reductions are apparent in the frontal white matter, whereas subcortically, hypertrophy is apparent in the basal ganglia, especially the putamen. Changes in the brain may be ongoing but asymptomatic, that is with minimal interference in functioning, making it difficult to diagnose HIV-associated neurocognitive disorders in the early stages.
Cognitive impairments associated with HIV occur in the domains of attention, memory, verbal fluency, and visuospatial construction. Specifically for memory, the lowered activity of the hippocampus changes the basis for memory encoding and affects mechanisms such as long-term potentiation. For example, patients with HIV have higher rates of clinical depression and alexithymia , i. Without combination antiretroviral therapy, cognitive impairments increase with successive stages of HIV.
The diagnosis of HIV-associated neurocognitive impairment is made using clinical criteria after considering and ruling out other possible causes. A study by Melrose et al. Participants in the study were diagnosed with HIV three months to sixteen years before the study. Ten out of eleven patients were on antiretroviral medication and none scored within the demented range on the HIV Dementia Scale.
There was reduced connectivity between the left caudate and ventral PFC and between the left caudate and dorsolateral PFC compared to healthy controls. In the control group, there was correlation between caudate activity and executive functioning as shown by performance on neuropsychological testing. The study by Melrose et al. Additionally, the anterior parietal activity showed a relationship with caudate functioning, which implicates a compensatory mechanism set forth when damage to the fronto-striatal system occurs.
Overall, the study by Melrose et al. Damage to the fronto-striatal system may underlie cognitive problems including executive function and sequencing tasks. Another area of impairment due to fronto-striatal dysfunction is in the area of emotion recognition.
The authors suggested that fronto-striatal abnormalities related to HIV may underlie these impairments. In identification tasks, administered by Clark et al. In the facial emotion task, fear recognition was significantly worse in the HIV than in the control group.
Mother-to-child transmission during pregnancy is the dominant mode of acquisition of HIV infection in children and has been associated with an increased risk of mortality and developmental delay. The main cells infected by HIV-1 in the nervous tissue are the microglia, astrocytes and macrophages , whereas infected neurons have been rarely observed.
The susceptibility to HIV-1 infection and replication in neuronal and glial cells is a function of cellular differentiation, and it is more likely in immature precursors than with differentiated cells.
Several soluble signals, such as cytokines , have been described to modulate susceptibility and can further contribute in supporting virus latency or virus replication during organ development. In fact, within the developing CNS, cells are under the control of environmental factors that provide instructive signals to neural cell targets.
By regulating the survival, differentiation and maintenance of specific functions of neuronal and glial precursors, these extracellular signals can influence many steps of the CNS development and concur in controlling virus-cell interactions in the maturing brain. In addition to the production of cytokines, HIV-1 infected mononuclear cells and astrocytes can produce a number of soluble mediators, including viral proteins such as gp and Tat, that can exert damaging effects on both developing and mature neural tissues.
Taken together, these observations suggest that the mechanism by which the virus can alter CNS development and induce pathology in the immature brain may depend upon the altered production of soluble bioactive compounds. Several potentially neurotoxic mediators have been identified in different model systems, including inflammatory cytokines, viral proteins and neurotoxic metabolites.
Thus, it is likely that a complex interaction of several mediators may alter the function and survival of actively developing and maturing cells, responsible for the neurologic disorders. From Wikipedia, the free encyclopedia.
Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments". Gendelman; I. Grant; I. Everall; S. Lipton; S. Indian J. Physicians India. Patients with HIV infection and untreated dementia have a worse prognosis average life expectancy of 6 mo than those without dementia. The primary treatment of HIV-associated dementia is antiretroviral therapy , which increases CD4 counts and improves cognitive function.
Supportive measures are similar to those for other dementias. For example, the environment should be bright, cheerful, and familiar, and it should be designed to reinforce orientation eg, placement of large clocks and calendars in the room. Measures to ensure patient safety eg, signal monitoring systems for patients who wander should be implemented.
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Common Health Topics. Videos Figures Images Quizzes. Commonly Searched Drugs. Symptoms and Signs. Test your knowledge. Peripheral nerve disorders can result from damage or dysfunction to the cell body, myelin sheath, axons, or neuromuscular junction.
Peripheral neuropathies can affect one or several sites in the body. Peripheral neuropathy due to ischemia is most likely to result in which of the following nervous system disorders? Add to Any Platform. Click here for Patient Education. Slowed thinking and expression. Clinical evaluation. Prompt evaluation, including MRI and usually lumbar puncture, when deterioration is acute.
Symptoms of dementia. These symptoms represent a decline from previous levels of functioning. These symptoms are not explained by delirium or a major psychiatric disorder.
HIV and Dementia | Johns Hopkins Medicine
It is a source of great morbidity and, when severe, is associated with limited survival. While its pathogenesis remains enigmatic in several important aspects, ADC is generally thought to be caused by HIV-1 itself, rather than to another opportunistic infection.
AIDS emphasizes its morbidity and poor prognosis, particularly when its severity is at stage 2 or greater see Table 1 , a severity comparable to other clinical AIDS-defining complications of HIV-1 infection. Dementia designates the acquired and persistent cognitive decline with preserved alertness that usually dominates the clinical presentation and determines its principal disability. Complex emphasizes that this disease not only impairs the intellect, but also concomitantly alters motor performance and, at times, behavior.
This involvement of the nervous system beyond cognition is evidence of a wider involvement of the CNS than occurs in some other types of dementia such as Alzheimer's disease. Additionally, myelopathy may be an important, indeed predominating, aspect of ADC, and organic psychosis may also be a feature in a subset of patients see Rheumatologic and Musculoskeletal Manifestations of HIV. These manifestations are therefore also encompassed within this term. By contrast, neither neuropathy nor functional psychiatric disturbance are included in ADC.
The designation is based on the degree of functional incapacity in cognitive and motor activities of work and daily living and ranges from stage 0. Those suffering stage 1 ADC usually do not consider their condition to be "minor. I prefer the simpler term "ADC," designating a subset as suffering a myelopathic variant when their signs and symptoms indicate isolated spinal cord dysfunction. ADC develops principally in the context of late HIV-1 infection and associated severe immunosuppression.
Its prevalence accordingly varies depending on the characteristics of the population sampled. Prospective studies have provided some clarification of the epidemiology and natural history of ADC stage 2 or higher , at least with respect to its more severe forms, in the era before combination highly active antiretroviral therapy HAART. Pathogenetically, these data suggest that severe immunosuppression has a strong "permissive" effect on the development of ADC, but alone is neither sufficient since many severely immunosuppressed patients do not develop the disorder nor absolutely necessary for ADC to manifest.
This poor prognosis for survival likely relates in part to the late stage of HIV-1 infection in which ADC develops, the concomitant susceptibility to other lethal complications of immunosuppression, limited effectiveness of antiviral treatments available at the time of the study, and the vulnerability of neurologic debility. The tendency for relatives and care givers to "give up" on such patients in the face of severe neurologic impairment may also influence this short survival.
Evidence supports a central role for HIV-1 in causing ADC, particularly in the subset of patients with more severe brain dysfunction see reviews[ 3, ]. Numerous studies have documented HIV-1 productive infection of macrophages and related microglia and nonproductive infection of a wider variety of cells, including particularly astrocytes.
Investigators have hypothesized that macrophage and microglial infection drives a chain of pathologic processes that eventuate in neuronal dysfunction.
Some of these effects are exerted directly on neurons while others involve intermediary cells to transduce and amplify these signals to eventuate in neurotoxicity. Particularly important in these sequences are activation of cytokine circuits, largely in macrophages and perhaps also astrocytes. Pathogenic cytokine activation and resulting neuropathologic sequelae can be considered as immunopathologic reactions that link infection to neurotoxicity.
The importance of understanding the individual mechanisms involved in these activation and neurotoxic reactions relates to the possibility that they may provide therapeutic targets.
Although the severity and relative prominence of some symptoms and signs compared to others may vary among individual patients, the general character of ADC involves three functional categories: cognition, motor performance, and behavior.
Of the three categories, cognitive and motor dysfunction are the most helpful in characterizing patients and in defining diagnosis; it is for this reason that they provide the basis of ADC Staging, which omits behavioral criteria.
When approaching diagnosis, it is useful to separately consider milder and more severe affliction. Cognitive impairment usually underlies patients' earliest symptoms.
Mildly afflicted patients most often have difficulty attending to more complex tasks at work or at home. They need to make lists, sometimes very detailed, of the day's activities.
They lose track of actions e. Processing unrelated or complex thoughts becomes slower and less facile. While similar lapses can trouble many normal people especially in the face of fatigue or generalized illness, lapses in ADC patients intrude on daily function to a greater degree.
Multi-staged tasks become difficult; e. When such dysfunction is mild, it may be difficult to substantiate the basis for these complaints by bedside examination, and it is important to apply tests that are sensitive to these abnormalities, including particularly tests requiring concentration, change of sets, and timed performance.
Because it was constructed for other conditions, the standard Mini-Mental Status 22 may not be sufficiently sensitive at this point; however, when ADC patients do perform abnormally, it is usually on reversals reversing a five-letter word like "world," or subtracting from by 7's , complex sequential tasks placing the right thumb on the left ear and sticking out the tongue , or remembering three objects.
Although motor symptoms are far less common during this early phase, individuals relying on rapid or fine coordination may note a change. For example, the guitarist may no longer be able to keep up with a difficult piece or the athlete may be slowed to below a competitive level. An inquiring history may discover a change in handwriting or, less commonly, clumsiness in tying shoes or buttoning a shirt. Moreover, even in those without overt symptoms, motor signs may be detected on examination, including slowing of attempts at rapid opposition of the thumb and forefinger, rotation of the wrist, or tapping of the toe.
While the gait may be generally steady, it is often slow, and rapid turns may be interrupted by an extra step or performed hesitantly. Reflexes are also often abnormal. The deep tendon stretch reflexes, including importantly the jaw jerk, are frequently hyperactive, although the ankle jerks may be relatively less active when there is concomitant polyneuropathy.
Babinski signs may be present and other "pathologic" release signs may also be detected; of these, the snout response is relatively frequent and particularly helpful when present in young patients. The time course and onset of milder ADC is variable. It may begin insidiously or abruptly and progress more rapidly to a higher stage, or it may continue to evolve slowly or even remain static for some period.
In patients with mild ADC, missed diagnosis usually results from overlooking the important aspects of the history. Functional difficulties may erroneously be considered as a "normal" part of systemic illness by patients and their caregivers despite the fact that most AIDS patients without neurologic conditions perform quite normally, even in the late stage of HIV-1 infection. Particularly important is the distinction of ADC from clinical depression, which can produce similar complaints but carries distinct therapeutic implications see Chapter 5.
Hypochondriasis and anxiety in those understandably worried about body function may also lead to similar complaints. In patients with more advanced disease, the principal exercise is in being certain that abnormal function relates to ADC rather than to another CNS disease.
Cognitive function in these subjects is clearly abnormal and obviously impairs functional status, although in patients with stage 2 or even 3 ADC who can maintain the civilities of casual conversation and personal interaction, it too can be missed by a cursory history and examination.
With more careful questioning of both the patient and associates, however, it is clear that stage 2 patients are too slow or forgetful to work, manage the household or, importantly, even maintain their own medications. They may get lost walking or driving and cannot be relied on to prepare meals, much less to balance the checkbook. On examination, a broader array of cognitive "domains" are afflicted. The bedside Mini-Mental Status is now often abnormal.
The components mentioned earlier, assessments of attention and concentration, are frequently impaired, and patients have trouble recalling three objects after 5 or 10 minutes. Timed activities are further slowed and attempts to draw complex objects may produce only simplified representations.
With increased severity, there is frank disorientation to time and place. Motor abnormalities may also become more clearly symptomatic and obvious to the patient's family and associates. Walking may be sufficiently unsteady to require a cane or someone alongside to prevent falling. Hyper-reflexia and pathologic reflexes are now almost always present, and gait instability and slowness is more clearly evident not just on turning, but even on the straightaway.
With further progression, ambulation constantly requires someone to balance and support the patient or is entirely precluded stage 3 or 4. Thinking and speaking also becomes slower and the content more impoverished. Concomitant behavioral changes may become more evident.
Patients appear duller and less vivacious. If left alone, they may sit still without spontaneously offering conversation, but only answering briefly in response to questions. This poverty of output and apathy may be mistaken for depression, but in most of these patients, dysphoria is absent, and disinterest and lack of initiative are the predominating aspects of behavior without sadness. A striking variant that manifests in a small minority of patients includes agitation with features of mania.
These patients usually exhibit a background of confusion that remains even as the hyperactivity is controlled by medication. The myelopathic variant of ADC has a distinct pathologic substrate, known as vacuolar myelopathy. Some of these patients may become wheelchair bound with normal or near normal cognition.
In others, the myelopathy is combined with cognitive difficulty. While the lower extremities are more severely affected than the arms, there is no distinct segmental level of spinal cord dysfunction. Rather, there is a gradual caudal increase in abnormality: knee tendon reflexes are more active than those in the arms, and gait or toe tapping are not performed as well as hand coordination tests or rapid finger movements.
Mild sensory loss is common, and is usually worse distally in the feet with impaired vibration and position sense most common; sensation is usually normal over the trunk and in the upper extremities. Because myelopathy is frequently combined with neuropathy, the cause of sensory loss in individual patients may not always be clear, and one often relies on the ankle tendon jerks to indicate the relative contribution of myelopathy increased ankle jerks or neuropathy decreased ankle jerks in the presence of increased patellar stretch reflexes.
Clinical presentation usually includes an ataxic and, sometimes, spastic gait. This disorder in children may be proportionally more important in the sense that it both occurs more commonly than in adults and results in even greater morbidity. Clinical presentation is with combined cognitive and motor dysfunction. Its etiology and pathogenesis are likely similar to the adult condition, although altered somewhat by involvement of the developing brain.
Treatment also follows a similar approach. Diagnosis of stage ADC is both an inclusionary and exclusionary exercise. It is important to understand that the distinct features of the syndrome described earlier in the chapter when occurring in the setting of late HIV-1 infection allow a positive diagnosis.
The combination of the characteristic cognitive dysfunction and symmetric motor abnormalities usually readily allows tentative diagnosis on the basis of the history and examination alone. There are a few other conditions that mimic the typical and uncomplicated presentation; some patients with primary CNS lymphoma located deep in the frontal white matter near the lateral ventricles, particularly when bilateral, may manifest a similar progressive dementia accompanied by motor slowing, apathy, impoverished speech output, and minimal lateralization.
Hydrocephalus can also produce a similar picture. In contrast, toxic and metabolic encephalopathies usually lead to a reduced level of arousal that is parallel to the cognitive deficiency rather than altering the latter in the face of full wakefulness as in ADC.
These disorders may coexist with and exacerbate ADC, however, and the combination can confuse diagnosis. ADC patients appear to be more sensitive to the side effects of neuroleptic agents, and subclinical ADC may explain the sensitivity of AIDS patients more generally to the extrapyramidal side effects of these drugs. Cytomegalovirus CMV encephalitis is one of the diagnostically more difficult conditions complicating late HIV-1 infections and may be difficult to distinguish from ADC.
Minor focal findings, including cranial nerve palsies and ataxia, may also accompany CMV encephalitis. Hyponatremia has also been noted more frequently in CMV encephalitis. An uncommon form of cerebral toxoplasmosis, the so-called encephalitic form, may be similarly confused with ADC as well as with CMV encephalitis.
This condition is caused by the acute development of multiple small toxoplasma abscesses throughout the brain, and may present with subacute global encephalopathy with few or no focal abnormalities. Once again, however, consciousness is usually depressed. Neurosyphilis is commonly considered in the differential diagnosis, although how often it clinically mimics ADC is uncertain. Viral serology, CSF profile, the presence of immunosuppression, and other ancillary findings usually allows distinction.