Neurologic signs and symptoms frequently manifest in acute HIV infection

Hellmuth, Joanna; Fletcher, James; Valcour, Victor; Kroon, Eugène; Ananworanich, Jintanat; Intasan, Jintana; Lerdlum, Sukalaya; Narvid, Jared; Pothisri, Mantana; Allen, Isabel Elaine; Krebs, Shelly J.; Slike, Bonnie M.; Prueksakaew, Peeriya; Jagodzinski, Linda L.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Spudich, Serena

doi:10.1212/wnl.0000000000002837

Cited by 58 publications

(39 citation statements)

References 27 publications

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“…Findings confirm early viral infection in the brain, often associated with neurological symptoms. [8,9] CNS inflammation increases, then is controlled by initiation of early therapy, surprisingly without evidence to date of neuronal injury. [10] These findings support emerging practices to start therapy as early as possible, and it will be important to follow the experience of these patients aggressively treated in the earliest days of infection.…”

Section: Acute Infectionmentioning

confidence: 99%

HIV-associated neurocognitive disorder

Clifford

2017

Current Opinion in Infectious Diseases

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Purpose of review HIV associated neurocognitive disease (HAND) is the most active topic for neuroAIDS investigations at present. Although impairment is mild in patients successfully treated with modern antiviral regimens, it remains an ongoing problem for HIV patients. It is important to update the emerging research concerning HAND. Recent findings The virus enters the brain during acute infection, with evidence for abnormal functioning that may occur early and often persists. Direct relationships with ongoing viral infection continue to be monitored, but chronic inflammation, often associated with monocytes and macrophages appear to be the most likely driver of cognitive dysfunction. Appreciation for cerebrovascular disease as a significant co-morbidity that is associated with cognitive deficits is increasing. Neuroimaging is actively being developed to address detection and measurement of changes in the brain. Optimal cART therapy has vastly improved neurologic outcomes, but so far has not been demonstrated to reverse the remaining mild impairment. Inflammatory and vascular mechanisms of cerebral dysfunction may need to be addressed to achieve better outcomes. Summary Ongoing research is required to improve neurological outcomes for persons living with HIV. It is likely that interventions beyond antiviral approaches will be required to control or reverse HAND.

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Section: Acute Infectionmentioning

confidence: 99%

HIV-associated neurocognitive disorder

Clifford

2017

Current Opinion in Infectious Diseases

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“…Several viral infections have been associated with GBS including cytomegalovirus (CMV), Hepatitis E virus (HEV) and Zika virus [ 4–6 ]. GBS can also occur with both acute and long-standing HIV infections [ 7 ]. The British HIV Association (BHIVA) guidelines state that a patient presenting with GBS should be screened for HIV [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

HIV positive patient with GBS-like syndrome

Shepherd¹,

Black

Thomson

et al. 2017

JMM Case Reports

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Introduction. Guillain–Barré Syndrome (GBS) is an acute demyelinating polyneuropathy which can occur post-infection. Criteria of diagnosis of GBS include areflexia with progressive bilateral weakness in arms and legs. GBS can lead to severe respiratory and cardiac complications. The fatality rate can be up to 5 % in patients, depending on the severity of the symptoms. HIV can cause a range of neurological disorders including, on rare occasions, GBS. GBS can occur at any stage of HIV infection, highlighting the complexity of diagnosis of GBS within HIV patients.Case presentation. A 57 year old female with lumbar back pain radiating to the legs, poor mobility and tiredness, with reports of a viral-like illness four days previously, was initially diagnosed with a lower respiratory tract infection and discharged. Seventeen days later the patient was readmitted to hospital with progressive lower and upper limb weakness, areflexia and sensory loss. She was diagnosed with GBS and was unexpectedly discovered to be HIV-positive. HIV avidity was low indicating a recently acquired HIV infection. The patient was treated with intravenous immunoglobulin for five days for the GBS and commenced antriretrovirals for HIV. The patient was discharge from hospital 53 days after admission with walking aids and regular physiotherapy follow-up.Conclusion. This case highlighted the need for all clinicians to be aware that patients with symptoms of GBS, regardless of clinical history should be offered an HIV test. GBS can be the first sign a patient is HIV-positive.

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“…The notion that therapeutic interventions during primary HIV infection can be an effective strategy to ameliorate the severity of disease in chronic stage has many precedents. Initiation of ART during early stages of HIV infection has proven beneficial in terms of improved brain metabolite levels and neuropsychological testing as well as preservation of mucosal Th17 function 5 , 21 – 23 . A similar approach to early intervention was used in the current study to dampen the establishment of a CNS niche for HIV by strengthening the BBB with the use of an Shh mimetic, SAG.…”

Section: Resultsmentioning

confidence: 99%

Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection

Singh

Piekna‐Przybylska

et al. 2017

Sci Rep

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Infiltration of infected leukocytes culminates in establishment of a brain niche for Human Immunodeficiency Virus (HIV) during acute phase of infection, initiating an ongoing cascade of persistent viral replication and inflammation, that causes irreversible neuronal injury and HIV associated neurocognitive disease (HAND). In this study, humanized mice were treated with Smoothened Agonist (SAG), a Sonic Hedgehog (Shh) mimetic in order to fortify blood brain barrier (BBB) and dampen leukocyte extravasation into CNS during AHI. Results indicate that SAG treatment reduced viral burden in the CNS immediately after HIV transmission, but also conferred extended neuroprotection via increased BBB integrity (elevated levels of tight-junction protein, Claudin 5, and reduced S100B levels in periphery). These mice also showed healthier neurons with thick, uniform dendrites and reduced numbers of activated astrocytes. Additional in vitro experiments suggested SAG treatment was not associated with the establishment or reversal of latency in the target cells. Altogether, these findings validate neuroprotective role of Shh signaling and highlight the therapeutic potential of Shh mimetics against CNS complications associated with HIV infection. Further our results strongly demonstrate that pharmacological interventions to reduce leukocyte mobilization during early HIV infection, can provide prolonged neuroprotection, which might significantly delay the onset of HAND.

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Neurologic signs and symptoms frequently manifest in acute HIV infection

Abstract: Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV.

Cited by 58 publications

References 27 publications

HIV-associated neurocognitive disorder

HIV-associated neurocognitive disorder

HIV positive patient with GBS-like syndrome

Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection

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