Persistent Undocumented Meningoencephalitis due to Histoplasmosis in an HIV-Infected Patient in Brazil.

Neurosyphilis During Acute HIV Infection: A CNS Immunologic and Virologic Characterization.

Antiretroviral drugs and the central nervous system.

Risk factors found in cerebrospinal fluid increase the likelihood that individuals with HIV disease will develop dementia or other neurocognitive disorders.

VP Shunt With Recurrent Malfunction in Two Pediatric Patients: Is the Hydrocephalus Truly Idiopathic?

BackgroundCentral nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection.MethodsProspective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1) progression of systemic infection, 2) CSF white blood cell (WBC) count, 3) antiretroviral therapy (ART), and 4) neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART.ResultsIn cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL). CSF HIV viral loads (VLs) correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts <50 cells/μL associated with a low prevalence of CSF pleocytosis and large differences between plasma and CSF VL. CSF HIV RNA correlated neither with the severity of the AIDS dementia complex (ADC) nor abnormal quantitative neurological performance, although these measures were associated with depression of CD4 counts.In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved.ConclusionCSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

OPINION Can research at the end of life be a useful tool to advance HIV cure? Sara Gianella a , Jeff Taylor b , Timothy R. Brown c , Andy Kaytes b , Cristian L. Achim a , David J. Moore a , Susan J. Little a , Ronald J. Ellis a and Davey M. Smith a,d AIDS 2017, 31:1–4 Keywords: end of life, eradication, HIV cure, last gift, legacy, peri-mortem research model, research Modern antiretroviral therapy (ART) has saved millions of years of life [1], but it cannot eradicate latently infected cells [2,3]. The replication-competent provirus that remains during ART represents the major barrier to curing HIV [4]. Most of this latent reservoir resides in solid tissues and not in circulating blood, and we have yet to fully define the sanctuary sites of HIV persistence [5]. Timothy Ray Brown (known by many as the ‘Berlin Patient’) may be the closest to an HIV cure after being treated with an allogeneic hematopoietic stem cell transplant from a donor who was homozygous for the CCR5D32 deletion [6]. Unfortunately, this remarkable success has not been reproduced, and robust viral replication resumes almost universally following treat- ment interruption [7–9]. Even if strategies currently in development succeed in purging HIV from circulating CD4 þ T cells, residual virus can remain in the central nervous system (CNS), gut-associated lymphoid tissue (GALT), genital tract, adipose tissue, and others [9–12]. Thus, cure efforts must tackle the eradication of HIV reservoirs in anatomic compartments and sanctuaries throughout the body. The earliest stages of HIV infection are characterized by high levels of viral replication and little immune response [13,14]. This window of uncontrolled replication allows the virus to seed reservoirs throughout the body, as early as within 2 weeks of HIV infection [15], and to persist indefinitely throughout the lifespan of HIV-infected individuals [10]. These proviral reservoirs continue to expand and diversify until viral replication is successfully suppressed with ART. Despite extensive investigations, we still do not fully understand the dynamics of the total body HIV reservoir and how sub-reservoirs in various compart- ments relate to one another. For example, it remains unclear what factors govern the size and the activity of replication-competent HIV DNA in the CNS compared to the genital tract and blood. Most studies that have explored nonblood reservoirs among persons living with HIV infection have been limited to small samples of cerebrospinal fluid (CSF), genital secretion, gut, and shallow lymph nodes [10,16]. Studies using macaque models with simian immunodeficiency viruses (SIVs) have been enlightening for reservoirs in different tissues [17–23], but while SIV shares a high degree of structural and sequence identity to HIV, studies of SIV will not suffice to test eradication strategies for humans. For example, the Merck adenovirus type 5 (Ad5) trivalent HIV-1 vaccine trial (STEP trial) did not show efficacy in preventing HIV infection or slowing disease progression [24], despite promising results in various macaques’ trials [25–27]. As the field tackles the ambitious goal of eradicating HIV from the human body, we will need to test the effectiveness of cure interventions in living persons. a University of California, San Diego, La Jolla, b Community Advisory Board (CAB) AntiViral Research Center (AVRC), c Las Vegas, Nevada, and d Veterans Affairs San Diego Healthcare System, San Diego, California, USA. Correspondence to Sara Gianella, University of California San Diego, 9500 Gilman Drive, MC 0679, La Jolla, CA 92093-0679, USA. Tel: +1 858 642 1620; fax: +1 858 552 7445; e-mail: gianella@ucsd.edu Received: 18 August 2016; revised: 23 September 2016; accepted: 27 September 2016. DOI:10.1097/QAD.0000000000001300 ISSN 0269-9370 Copyright Q 2016 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

HIV-1 infects the central nervous system (CNS) and may cause AIDS dementia complex (ADC) and other neurologic complications. The cerebrospinal fluid (CSF) virus load is usually 0,5 -1 log lower than in blood, but in some patients the CSF quantitative HIV-1 RNA values exceed the paired blood samples. CSF neopterin concentrations are increased in all stages of HIV-1 infection, with the highest concentrations in AIDS patients and patients with CNS opportunistic infections. CD4 cell count and quantitative HIV RNA PCR tests in peripheral blood are used in clinical practice to monitor the HIV-1 infection and the anti-retroviral treatment effect. In most patients the anti-retroviral treatment response is similar in the cerebrospinal fluid (CSF) compare to the peripheral blood and the CSF viral load and neopterin concentrations are markedly reduced following treatment. ADC has become a rare complication. In spite of virological effective treatment many patients have a low grade intrathecal immunoactivation, measured as CSF neopterin concentrations above the 95% confidence interval found in IIIV-1 negative controls, after such a long time as after 2 years of anti-retroviral treatment. The risk of long term intrathecal immunoactivation and which anti-retroviral combination treatment has the best effect on CSF parameters is not known. CSF neopterin concentrations are at present not used in clinical practice but may add valuable information.

Case presentation: Patient 1: A 68-year-old woman presented in 2008 with progressive lower limb weakness that progressed to wheelchair dependence in less than 3 years, accompanied by a 30 kg weight loss over 2 years. Motor strength examination revealed proximal (MRC grade 2) and distal (MRC grade 4) weakness in the lower limbs, along with proximal atrophy. In the upper limbs, proximal weakness (MRC grade 4) was observed. Osteotendinous reflexes were preserved, except for the abolished patellar reflex. Plantar cutaneous reflexes showed flexion. Laboratory tests indicated normal CPK and aldolase levels, but serology was positive for HTLV-1. Cerebrospinal fluid (CSF) analysis confirmed HTLV-1 positivity. Electromyography (EMG) demonstrated asymmetric proximal myopathy, more severe in the lower limbs, with early recruitment and small amplitude potentials. A muscle biopsy indicated inclusion body myositis, showing CD8+ cells and macrophages surrounding and invading non-necrotic fibers, rimmed vacuoles, mitochondrial alterations, and protein aggregates. Patient 2: A 59-year-old man reported reduced strength in his lower limbs, particularly the left leg, for several years without knowing the exact onset. Significant limitations became apparent after 2020, when he required unilateral support to walk. Motor strength examination revealed MRC grade 4 weakness in the right lower limb and MRC grade 3 in the left. Atrophy, fasciculations, spasticity in the lower limbs, and signs of pyramidal release were noted in all four limbs. He walked with a scissor gait, more severe on the left side, using unilateral support. HTLV serology was positive. MRI did not indicate myelopathy. Electroneuromyography (ENMG) met the criteria for diffuse lower motor neuron involvement (four segments) with active denervation and chronic reinnervation, classifying this case within the HTLV-ALS spectrum. Discussion: There are several clinical and radiological presentations of neuromuscular diseases related to HTLV-1, as seen in our cases. The most frequent complications are tropical spastic paraparesis/myelopathy (HAM/TSP) and adult T-cell leukemia/lymphoma (ATL). Some cases of HAM/TSP mimic ALS (Amyotrophic Lateral Sclerosis), potentially leading to diagnostic confusion, though differing mainly in autonomic and sensory symptoms in addition to the bulbar segment. Inflammatory myositis associated with HTLV-1 has few reported cases despite in vitro evidence of myotoxicity by the virus. So far, there are several case reports of patients with IBM and HTLV-I infection. In addition, we have polyneuropathy also composing other neuromuscular presentations described with HTLV. Final comments: Both patients in these cases exhibit rare complications related to chronic HTLV-1 infection, highlighting the importance of clinical reasoning for accurate investigation given the wide range of differential diagnoses.

Pseudomeningocele (PMC) is a rare complication of cervical spine surgery, typically manifesting as an abnormal cerebrospinal fluid (CSF) collection in the paraspinal tissues. We present a unique case of a 39-year-old male who developed recurrent symptomatic pseudomeningocele following surgical excision of a C5-T1 intramedullary subependymoma. The patient initially presented with progressive weakness in the lower limbs and upper motor neuron signs. Following primary tumor excision and fixation (C5-T1 laminectomy, excision, biopsy, and fusion on 20.02.2023), the patient developed postoperative pseudomeningocele with significant neurological deficit. Revision surgery for pseudomeningocele repair was performed, yet the collection persisted. Despite persistent CSF collection on imaging, the patient showed progressive neurological recovery with conservative management including acetazolamide therapy and physiotherapy. The patient now demonstrates substantially improved motor power with residual symptoms of postural headaches and giddiness. This case highlights the variable clinical course of pseudomeningocele and the potential for neurological recovery despite persistent imaging findings, as well as the effectiveness of conservative management with pharmacological and rehabilitative interventions. Keywords: Pseudomeningocele, Intramedullary tumor, Cervical spine surgery, Subependymoma, CSF leak, Acetazolamide

Case presentation: Case 1: A 30-year-old HIV-infected woman with a history of pulmonary tuberculosis presented to Hospital São Lucas with paresthesia and weakness in her lower limbs for 2 weeks. She had been on lamivudine, stavudine, and efavirenz for 10 months. Neurological examination showed grade 3 weakness in lower limbs and absent deep tendon reflexes. Her CD4 count was 229/mm³, and viral load was undetectable. Within 10 days, symptoms progressed to lower and upper limbs, with lactic acidosis (up to 9.3 mmol/L) and autonomic dysfunction. Normal brain CT and CSF analysis, but nerve conduction studies indicated severe axonal sensorimotor polyneuropathy. HAART was discontinued, and she received ICU care with IVIG therapy. She developed respiratory failure, requiring mechanical ventilation and tracheostomy. Over 3 months, her symptoms improved, and she had only mild weakness and was discharged in with normal lactate levels. Case 2: A 44-year-old HIV-positive woman on stavudine, lamivudine, and efavirenz for 1 year was admitted with nausea, vomiting, stomachache, and diarrhea for 7 days. Her CD4 count was 130/mm³. Initial evaluations were normal, but abdominal x-ray showed bowel distension. Surgical evaluation ruled out acute pathology, and endoscopy revealed duodenitis. After 10 days, she developed symmetric lower limb paresthesia and increased lactate levels (7.5mmol/L). Stavudine was discontinued, and riboflavin was started. Symptoms progressed to involve the upper limbs and cervical region, with hypotension and tachycardia. Lactate levels rose to 10.1 mmol/L, prompting ICU transfer. She developed respiratory failure with visual symptoms, tachypnea, and diaphoresis. Neurological exam showed generalized areflexia, ascending paresis, diplopia, and bitemporal hemianopsia. Mechanical ventilation was initiated, and IVIG commenced. Nerve conduction showed severe axonal sensorimotor polyneuropathy. She was discharged after 44 days without neurological deficits, continuing medication. Lactate levels normalized to 1.1 mmol/L. Discussion: HIV-associated neuromuscular weakness syndrome (HANWS) is a rare neuromuscular syndrome linked to hyperlactatemia and exposure to stavudine and/or didanosine. Severe hyperlactatemia and lactic acidosis are rare but serious complications of antiretroviral therapy, associated with dideoxynucleoside exposure, female gender, advanced immunosuppression, and possibly ethnicity. The pathogenesis of this neuromuscular syndrome in HIV-infected patients is likely multifactorial, involving mitochondrial and immunological mechanisms associated with both HIV infection and HAART. Treatment strategies for HANWS remain uncertain yet critical due to its potentially fatal nature. Most patients exhibit axonal alterations; however, the presence of demyelinating findings may guide therapeutic decisions, suggesting the possible use of intravenous immunoglobulin or plasmapheresis. Neurologists must maintain vigilance for diagnosing this syndrome promptly.

4.0 When to start

Choriocarcinoma is a highly malignant trophoblastic neoplasia, arising following any type of pregnancy. Even though choriocarcinoma has an early haematogenous metastasis to multiple organs, spinal metastasis is extremely rare. A 28-year-old woman presented with a two-week history of progressive numbness and weakness of the lower limbs and difficulty in walking. In magnetic resonance imaging of the spine, soft tissue components were noted adjacent to the spinal cord. She underwent laminectomy to remove the extramedullary located tumour mass, which was compressing the spinal cord. Although there was a significant improvement in tactile stimulation in the lower limb following six courses of multi-agent chemotherapy, she continued to have leg weakness. Despite improvements in treatment modality and the use of combined modality treatment with chemotherapy, surgery, and radiation, the prognosis for this choriocarcinoma with spinal metastasis is unfavourable. Earlier diagnosis and multimodality treatment is crucial for a significant reduction in mortality and morbidity.

P5.22 Granulomatous myositis and inclusion bodies myositis in a patient with hepatitis C

A novel homozygous mutation in ERLIN1 gene causing spastic paraplegia 62 and literature review

Chronic inflammatory demyelinating polyneuropathy in a 13-year-old girl: A case report