Editor's Choice - Very Urgent Carotid Endarterectomy is Associated with an Increased Procedural Risk: The Carotid Alarm Study.

OBJECTIVE/BACKGROUND: The aim of the Carotid Alarm Study was to compare the procedural risk of carotid endarterectomy (CEA) performed within 48 hours with that after 48 hours to 14 days following an ipsilateral cerebrovascular ischaemic event. METHODS: Consecutive patients with symptomatic carotid stenosis undergoing CEA were prospectively recruited. Time to surgery was calculated as time from the most recent ischaemic event preceding surgery. A neurologist examined patients before and, after CEA. The primary endpoint was the composite endpoint of death and/or any stroke within 30 days of the surgical procedure. The study was designed to include 600 patients, with 150 operated on within 48 hours. RESULTS: From October 2010 to December 2015, 418 patients were included, of whom 75 were operated within 48 hours of an ischaemic event. The study was prematurely terminated owing to the slow recruitment rate in the group operated on within 48 hours. Patients undergoing CEA within 48 hours had a higher risk of reaching the primary endpoint than those operated on later (8.0% vs. 2.9%). Multivariate logistic regression analyses showed that CEA performed within 48 h (odds ratio [OR] 3.07; 95% confidence interval [CI] 1.04-9.09), CEA performed out of office hours (OR 3.65; 95% CI 1.14-11.67), and use of shunt (OR 4.02; 95% CI 1.36-11.93) were all independently associated with an increased risk of reaching the primary endpoint. CONCLUSION: CEA performed within 48 hours was associated with a higher risk of complications compared with surgery performed 48 hours-14 days after the most recent ischaemic event.

Impact of the Swedish National Stroke Campaign on stroke awareness.

BACKGROUND: Time delay from stroke onset to arrival in hospital is an important obstacle to widespread reperfusion therapy. To increase knowledge about stroke, and potentially decrease this delay, a 27-month national public information campaign was carried out in Sweden. AIMS: To assess the effects of a national stroke campaign in Sweden. METHODS: The variables used to measure campaign effects were knowledge of the AKUT test [a Swedish equivalent of the FAST (Face-Arm-Speech-Time)] test and intent to call 112 (emergency telephone number) . Telephone interviews were carried out with 1500 randomly selected people in Sweden at eight points in time: before, three times during, immediately after, and nine, 13 and 21 months after the campaign. RESULTS: Before the campaign, 4% could recall the meaning of some or all keywords in the AKUT test, compared with 23% during and directly after the campaign, and 14% 21 months later. Corresponding figures were 15%, 51%, and 50% for those remembering the term AKUT and 65%, 76%, and 73% for intent to call 112 when observing or experiencing stroke symptoms. During the course of the campaign, improvement of stroke knowledge was similar among men and women, but the absolute level of knowledge for both items was higher for women at all time points. CONCLUSION: The nationwide campaign substantially increased knowledge about the AKUT test and intention to call 112 when experiencing or observing stroke symptoms, but knowledge declined post-intervention. Repeated public information therefore appears essential to sustain knowledge gains.

Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis.

BACKGROUND AND PURPOSE: Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. METHODS: Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. RESULTS: The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. CONCLUSION: In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.

Psychometric properties of the Satisfaction With Life Scale in Parkinson's disease.

OBJECTIVE: The Satisfaction With Life Scale (SWLS) is a global measure of life satisfaction (LS). The objective of this study was to evaluate the psychometric properties (data completeness, scaling assumptions, targeting and reliability) of the SWLS in a sample of people with Parkinson's disease (PD). MATERIALS AND METHODS: A postal survey including a Swedish version of the SWLS and demographic information was administered to 174 persons with PD; 97 responded and received a second survey after 2 weeks. RESULTS: The mean (SD) age and PD duration of the 97 responders were 73 (8) and 7 (6) years, respectively. Data completeness was 92% to 97% for the five items in the SWLS and 92% for the total score (5-35 points). The mean score of the SWLS was 24.2 points (7.7), indicating that this group had an average LS. The items' means and SDs were roughly parallel and the score distribution was even. The internal consistency reliability (Cronbach's alpha) was 0.90. The test-retest reliability, assessed by the intraclass correlation coefficient, was 0.78. The scale showed no systematic difference between the first and second response. The standard error of measurement was 3.6 points, and the smallest detectable difference was 10.0 points. CONCLUSIONS: This evaluation of the psychometric properties of the SWLS shows that the scale has good data completeness, scaling assumptions and targeting and that the internal consistency reliability and the test-retest reliability are acceptable. Thus, the SWLS is a psychometrically sound and suitable tool to asses LS in people with PD.

Public stroke awareness and intent to call 112 in Sweden.

BACKGROUND AND AIMS: Recognition of stroke symptoms and activation of emergency services are essential in minimizing delay for acute stroke treatments. In this study, we assessed public stroke awareness in Sweden. METHODS: One thousand and five hundred residents aged 18-79 years participated in a telephone survey. Open-ended questions were used to assess knowledge of stroke symptoms, risk factors, and action if witnessing or experiencing a potential stroke. RESULTS: Seventy-two percentage could report at least one stroke symptom and 86% at least one risk factor. Only 13% could report three or more stroke symptoms. Female sex (OR, 1.79; 95% CI, 1.30-2.45) and high education (OR, 2.30; 95% CI, 1.38-3.80) were associated with knowledge of stroke symptoms. Sixty-five percentage indicated they would call the emergency number 112 if witnessing or experiencing a potential stroke. Female sex (OR, 1.48; 95% CI, 1.18-1.85) and high education (OR, 1.40; 95% CI, 1.01-1.93) were positively associated, while increasing age (OR, 0.99; 95% CI, 0.98-0.99) was negatively associated with intent to call 112. CONCLUSION: We confirm a rather low public awareness of stroke in Sweden, poorer among males and those with low education. With increasing age, a lower proportion indicated intent to call 112 for stroke symptoms.

Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis.

The major intermediate cytoskeletal protein of astrocytes, glial fibrillary acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). Patients with relapsing-remitting MS (RRMS, n = 15) or secondary progressive MS (SPMS, n = 10) and healthy control subjects (n = 28) were examined twice with an interval of 8-10 years apart. Neurological deficits were scored with the Expanded Disability Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (r and r (s) = 0.50, p = 0.006). Adjusting for age, MS patients had increased GFAP levels compared with controls (p = 0.03) and GFAP levels correlated with neurological disability (EDSS, r = 0.51, p < 0.05) and disease progression [Multiple Sclerosis Severity Score (MSSS), r = 0.47, p < 0.05]. The mean annual increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9 ng/L for SPMS patients. GFAP level at the first examination had predictive value for neurological disability 8-10 years later (EDSS, r = 0.45, p < 0.05) but not for EDSS increase between the examinations. NFL levels were not significantly increased in MS patients compared with controls and had no relationship to disability or progression and no prognostic value for disability development. GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and may have a role in clinical trials for assessing the impact of therapies on MS progression.

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease.

OBJECTIVES: Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non-specific marker of neuronal damage, are normal in Parkinson's disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF-NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. MATERIALS AND METHODS: CSF-NFL levels were measured consecutively in eight patients with PD before and after STN-DBS treatment. RESULTS: CSF-NFL levels were normal prior to STN-DBS and increased sharply during the first 2 weeks post-operatively, but normalized after 12 months or more. CONCLUSION: The STN-DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF-NFL levels at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term STN-DBS stimulation.

No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.

BACKGROUND: Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. OBJECTIVE: To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. MATERIALS AND METHODS: Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. RESULTS: The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. DISCUSSION: Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.

Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) Farm Program: results from finisher pig surveillance.

In 2006, the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) Farm Program was implemented in sentinel grower-finisher swine herds in Québec, Ontario, Manitoba, Saskatchewan and Alberta. Herds were visited 1-3 times annually. Faecal samples were collected from pens of close-to-market (CTM) weight (>80 kg) pigs and antimicrobial use (AMU) data were collected via questionnaires. Samples were cultured for generic Escherichia coli and Salmonella and tested for antimicrobial susceptibility. This paper describes the findings of this program between 2006 and 2008. Eighty-nine, 115 and 96 herds participated in this program in 2006, 2007 and 2008 respectively. Over the 3 years, antimicrobial resistance (AMR) levels remained consistent. During this period, resistance to one or more antimicrobials was detected in 56-63% of the Salmonella spp. isolates and 84-86% of E. coli isolates. Resistance to five or more antimicrobials was detected in 13-23% of Salmonella and 12-13% of E. coli. Resistance to drugs classified as very important to human health (Category I) by the Veterinary Drug Directorate (VDD), Health Canada, was less than or equal to 1% in both organisms. AMU data were provided by 100 herds in 2007 and 95 herds in 2008. Nine herds in 2007 and five herds in 2008 reported no AMU. The most common route of antimicrobial administration (75-79% of herds) was via feed, predominantly macrolides/lincosamides (66-68% of herds). In both 2007 and 2008, the primary reasons given for macrolide/lincosamide use were disease prevention, growth promotion and treatment of enteric disease. The Category I antimicrobials, ceftiofur and virginiamycin were not used in feed or water in any herds in 2008, but virginiamycin was used in feed in two herds in 2007. Parenteral ceftiofur was used in 29 herds (29%) in 2007 and 20 herds (21%) in 2008. The reasons for ceftiofur use included treatment of lameness, respiratory disease and enteric disease.

Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study.

BACKGROUND AND PURPOSE: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. METHODS: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. RESULTS: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. CONCLUSIONS: The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.

Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis.

OBJECTIVE: To test the hypothesis that the arachodinic acid metabolites prostaglandin E2 (PGE2) and 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in cerebrospinal fluid (CSF) are elevated and reflect neuroinflammation and degenerative changes in multiple sclerosis (MS). PATIENTS AND METHODS: We measured PGE2 and 15(S)-HETE concentrations, as well as markers of axonal and astroglial injury in CSF from 46 MS patients, 46 healthy siblings and 50 controls. RESULTS: We found elevated levels of both PGE2 and 15(S)-HETE in MS compared with the control and sibling groups. Siblings had lower PGE2 levels and higher 15(S)-HETE levels than controls. There were no correlations between either PGE2 or 15(S)-HETE and clinical scores of MS severity or biochemical markers of axonal or astroglial injury. CONCLUSION: These data suggest no direct involvement of PGE2 and 15(S)-HETE in the MS disease process. Rather, the elevated levels reflect a general up-regulation of arachidonic acid metabolism and neuroinflammation.

Apolipoprotein E polymorphism and gender difference in outcome after severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is one of the most common causes of death and dismal outcome among children and young adults. The morbidity and mortality differ but more aggressive monitoring and more designated neuro intensive care units have improved the results. Studies have demonstrated a connection between apolipoprotein E (APOE) genotype and outcome after TBI, but few are prospective and none is from northern Europe. APOE has three alleles: epsilon2, epsilon3 and epsilon4. METHODS: A total of 96 patients with Glasgow coma score (GCS) < or =8 were prospectively and consecutively included. APOE genotypes were all analyzed at the same laboratory from blood samples by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: All patients were assessed at 1 year with Glasgow outcome scale extended (GOSE), National Institute of Health Stroke Scale (NIHSS) and the Barthel daily living index. The genotype was available in all patients. Twenty-six patients expressed APOE epsilon4 while 70 patients did not. Outcome demonstrated that patients with APOE epsilon4 had worse outcome vs. those lacking this allele. When subdividing patients into gender, males with APOE epsilon4 did worse, a difference not detected among female patients. CONCLUSIONS: APOE epsilon4 correlated to worse outcome in TBI patients. We also found that males with APOE epsilon4 had poor outcome while females did not. Thus, the results indicate that genetic polymorphism may influence outcome after TBI.

Serum levels of S100B, S100A1B and S100BB are all related to outcome after severe traumatic brain injury.

OBJECTIVES: S100B is an established marker of brain damage. Used in the context as a biochemical marker, S100B denotes a measurement of all S100 proteins, including at least one S100B monomer, i.e. the sum of the two dimers S100A1B and S100BB. Almost all published studies are based on this "sum concentration". However, the brain specificity of S100B has been questioned and increased serum levels have also been reported after trauma without head injury. Since the S100B monomer dominates in the brain, we hypothesised that the S100BB dimer should be better related to outcome after severe traumatic brain injury than S100A1B or the "sum concentration". METHODS: Daily serum samples were collected from 59 patients with severe traumatic brain injury. Three different ELISA methods were used for measurements of S100B, S100A1B and S100BB respectively. Outcome was assessed after one year and categorised according to the Glasgow Outcome Scale. RESULTS: Serum levels of S100B, S100A1B and S100BB followed the same temporal course, with early maximum and rapidly decreasing values over the first days after the trauma. Maximum serum concentrations of each of the parameters were increased in the patient group with an unfavourable outcome compared with those with a favourable outcome (p = 0.01, 0.006 and 0.004, respectively). CONCLUSION: Both S100A1B and S100BB were related to outcome after severe traumatic brain injury. Even though this study is small, it seems unlikely that separate analyses of the dimers are of any advantage compared with measuring S100B alone.

Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and beta-arrestin1.

The insulin-like growth factor 1 receptor (IGF-1R) is crucial for growth and survival of malignant cells. Experience in targeting IGF-1R in cancer models has shown that strategies promoting downregulation of the receptor are much more efficient in inducing apoptosis than those inhibiting the IGF-1R activity. Recently, we found that the cyclolignan picropodophyllin (PPP) inhibits phosphorylation of IGF-1R and activation of downstream signaling without interfering with the highly homologous insulin receptor (IR). Furthermore, PPP treatment caused strong regression of tumor grafts and prolonged survival of animals with systemic tumor disease. Here we demonstrate that PPP also downregulates the IGF-1R, whereas the IR and several other receptors were not affected. PPP-induced IGF-1R downregulation required expression of the MDM2 E3 ligase, which recently was found to ubiquitinate and cause degradation of the IGF-1R. In addition knockdown of beta-arrestin1, the adaptor molecule known to bridges MDM2 and IGF-1R, prevented downregulation of the receptor and significantly decreased PPP-induced cell death. All together these data suggest that PPP downregulates IGF-1R by interfering with the action of beta-arrestin1/MDM2 as well as the achieved receptor downregulation contributes to the apoptotic effect of PPP.

Serum levels of glial fibrillary acidic protein correlate to tumour volume of high-grade gliomas.

OBJECTIVES: To investigate serum levels of glial fibrillary acidic protein (GFAP) and S-100B in patients with newly diagnosed high-grade gliomas. MATERIALS AND METHODS: GFAP and S-100B were measured by enzyme-linked immunosorbent assay techniques in preoperative serum from 31 patients with high-grade gliomas. A database with clinical, radiological and histological variables was created for statistical analyses. RESULTS: Mean serum levels of 239 ng/l (range 30-1210 ng/l) for GFAP and 58.3 ng/l (range 22-128 ng/l) for S-100B were found. Of the 31 patients, 16 had elevated levels of GFAP while only two showed increased S-100B concentrations. Tumour size was the only variable significantly associated with serum levels of GFAP (P < 0.0001) with a linear correlation coefficient of 0.67. CONCLUSIONS: Serum levels of GFAP demonstrated a linear correlation to tumour volume in patients with high-grade gliomas. GFAP seems to be a more reliable biomarker in patients with high-grade gliomas than the commercially available S-100B.

Mid-life adiposity factors relate to blood-brain barrier integrity in late life.

OBJECTIVE: We explored the relationship between adiposity factors measured during mid-life and blood-brain barrier (BBB) integrity measured via the cerebrospinal fluid/serum (CSF/S) albumin ratio in late life. Adiposity factors included body mass index and blood levels of sex hormone binding globulin (SHBG) and leptin. Design. Retrospective analyses over 24 years within a longitudinal study. SETTING: Population-based sample. Subjects. Eighty-one women. MAIN OUTCOME MEASURES: CSF/S albumin ratio. RESULTS: The CSF/S albumin ratio measured at age 70-84 years was higher amongst women who were overweight or obese (6.50 +/- 2.79 vs. 5.23 +/- 1.61, age-adjusted P = 0.012), and was inversely correlated with SHBG (age-adjusted r = -0.321, P < 0.005) at age 46-60 years. In stepwise regression models, SHBG predicted the CSF/S albumin ratio (beta = -0.017, R2 = 0.107, P = 0.007). The best model (R2 = 0.187) predicting CSF/S albumin ratio included SHBG, age group (age 46 years versus >46), overweight or obesity, and an age group by SHBG interaction. CONCLUSIONS: Lower levels of SHBG in mid-life were related to worse BBB integrity in women after 24 years in late life, even considering other adiposity factors. SHBG may be important for understanding sex hormone-mediated mechanisms in brain health or as an independent marker of adipose tissue, the largest endocrine organ.

CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus.

BACKGROUND - To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects. METHODS - Lumbar CSF concentrations of sulfatide, neurofilament protein light (NFL), total-tau (T-tau), hyperphosphorylated tau (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analysed. RESULTS - The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery. CONCLUSIONS - The most striking finding was the power of the combined pattern of NFL, P-tau, and Abeta42 in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly.

Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection.

OBJECTIVE: Increased levels of the light-chain neurofilament protein (NFL) in CSF provide a marker of CNS injury in several neurodegenerative disorders and have been reported in the AIDS dementia complex (ADC). We examined the effects of highly active antiretroviral treatment (HAART) on CSF NFL in HIV-1-infected subjects with and without ADC who underwent repeated lumbar punctures (LPs). METHOD: NFL was measured by ELISA (normal reference value < 250 ng/L) in archived CSF samples from 53 patients who had undergone LPs before and after initiation of HAART. RESULTS: Twenty-one of the subjects had increased CSF NFL at baseline, with a median level of 780 ng/L and an intraquartile range (IQR) of 480 to 7300. After 3 months of treatment, NFL concentrations had fallen to normal in 48% (10/21), and the median decreased to 340 ng/L (IQR < 250 to 4070) (p < 0.001), whereas at 1 year, only 4 of 16 of the 21 subjects observed for this length still had elevated NFL levels. Thirty-two subjects had normal NFL at baseline, and all but one remained normal at follow-up. These effects on CSF NFL were seen in association with clinical improvement in ADC patients, decreases in plasma and CSF HIV-1 RNA and CSF neopterin, and increases in blood CD4 T cell counts. CONCLUSION: HAART seems to halt the neurodegenerative process(es) caused by HIV-1, as shown by the significant decrease in CSF NFL after treatment initiation. CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy.