Serum uric acid levels and their correlation with clinical and cerebrospinal fluid parameters in patients with neuromyelitis optica

Although uric acid (UA) concentration has been considered a surrogate marker for monitoring the progression of multiple sclerosis (MS), less is known about the relationship between UA and the progression of neuromyelitis optica (NMO). We therefore investigated the correlations between serum UA concentrations and the clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors assessed in patients with NMO included gender, disease duration, disease disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24 hour immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean serum UA concentrations were compared in patients with NMO and in a control group of patients with cerebral infarction (CI). We found that mean serum UA concentrations were significantly lower in patients with NMO compared to those with CI (206.81 compared to 274.00 μmol/L, p = 0.00). Serum UA concentration was correlated directly with NMO duration (p = 0.013) and was inversely correlated with the Expanded Disability Status Scale score (p = 0.021). Patients with NMO with lower serum UA concentrations tended to be positive for OB, to have higher CSF protein and MBP concentrations, and to have higher WBC counts and 24 hour IgG index, but no correlation was statistically significant. UA may be a useful surrogate marker for monitoring NMO activity.     

Common CYP7A1 promoter polymorphism associated with risk of neuromyelitis optica

Neuromyelitis optica (NMO) is a severe idiopathic inflammatory disease of the central nervous system primarily affecting the optic nerves and spinal cord. In this study, we generated genome-wide SNP data from NMO patients and normal controls (53 cases and 240 controls), and followed up on the association signals with samples from a larger number of inflammatory demyelinating diseases, including NMO (n = 93), multiple sclerosis (MS, n = 71), idiopathic recurrent transverse myelitis (IRTM, n = 57), and normal controls (n = 240). Statistical analyses revealed that a common promoter SNP in CYP7A1 has a protective/gene dose-dependent effect on the risk of NMO (P = 0.0004). A stronger association between the variables and subsequently, a higher protective effect (lower OR) on the risk of NMO were observed among patients carrying the “G/G” genotype of rs3808607 than those with the “T/G” genotype (OR = 0.38/P = 0.01 vs. OR = 0.12/P = 0.0004, respectively). The associations which were only observed in patients with NMO suggest that there are differences in the genetic etiology of the inflammatory demyelinating diseases (NMO, classical MS, and IRTM).     

Infectious and immune-mediated central nervous system disease in 48 COVID-19 patients

ObjectivesTo summarise and discuss current knowledge about SARS-CoV-2-associated infectious/immune-mediated central nervous system (CNS)-disease.MethodLiterature review.ResultsAltogether 28 articles were found, which reported 48 patients with SARS-CoV-2-associated infectious/immune-mediated CNS-disease. Age ranged from 22 to 79y. There was male preponderance. There were 14 patients with infectious CNS-disease (meningitis (n = 1), encephalitis (n = 5), meningo-encephalitis (n = 5), myelitis (n = 3)), and 34 patients with parainfectious CNS-disease (encephalopathy (n = 18), autoimmune encephalitis (n = 11), acute, disseminated, encephalo-myelitis (n = 3), acute, haemorrhagic, necrotizing encephalopathy (n = 2)). The cerebrospinal fluid (CSF) was tested for SARS-CoV-2 in 40 patients and was positive for the virus in 4 patients with infectious CNS-disease but was negative for the virus in all patients with parainfectious CNS-disease. Immune-modulating treatment may be more effective than virostatics/antibiotics for SARS-CoV-2-associated infectious/parainfectious, non-vascular, non-hypoxic CNS-disease. In patients with autoimmune encephalitis plasmapheresis may be beneficial. Twenty-two patients recovered, 2 did not, and 6 patients died.ConclusionsSARS-CoV-2 can cause infectious/immune-mediated CNS-disease. The CSF is positive for virus-RNA in only few patients with infectious CNS-disease but negative for virus-RNA in immune-mediated CNS-disease, suggesting an immune-mediated pathophysiological mechanism. The outcome of SARS-CoV-2-associated infectious/immune-mediated CNS-disease is favourable in the majority of cases but can be fatal in single cases.     

Medullary hemangioblastoma: 34 patients at a single institution

This study aimed to elucidate the surgical experience of medullary hemangioblastoma (MH) at a single institution. We reviewed 34 consecutive patients with MH operated on between January 2005 and June 2012 in the neurosurgery department of the Beijing Tiantan Hospital. There were 14 men and 20 women. The patients were aged from 17 to 60 years with an average age of 38 years. Tumors were cystic in 12 patients (Type A), and solid in 22 patients. The solid tumors were of a small size in six patients (<3 cm, Type B), large in 12 (3.1–5 cm, Type C), and giant in four (>5 cm, Type D). Radical tumor removal was achieved in all patients. Tracheotomy was performed in 10 patients (one Type B patient, seven Type C, two Type D) postoperatively. Pneumonia secondary to lower cranial nerve palsy occurred in six patients (all Type C). Complications including intracranial infection (n = 5), gastrointestinal bleeding (n = 2), and intracranial hematoma (n = 1) also occurred in this group. Follow-up (range, 2–82 months; mean, 30 months) was available in all patients. At follow-up, 29 patients (85.3%) had a good outcome. Twenty-eight of these (82.4%) had an excellent outcome postoperatively (Karnofsky Performance Status ⩾80). Although transient surgical complications are possible especially for large solid tumors, total surgical resection can be performed with favorable long-term outcomes with meticulous microsurgical technique and understanding of the vascular pattern of the tumor. Postoperative management of MH is as important as the operation.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

The role of aquaporin-4 antibodies in Chinese patients with neuromyelitis optica

We determined the presence of aquaporin-4 (AQP4) antibodies by indirect immunofluorescence in human AQP4-transfected cells, and evaluated the diagnostic and prognostic relevance of AQP4 antibodies in 210 Chinese patients with neuromyelitis optica (NMO), high-risk NMO (HR-NMO), classic multiple sclerosis (MS), and other neurologic diseases. Patients were enrolled from The General Hospital of the Chinese People’s Liberation Army and followed-up for a median of 2 years. The patients with HR-NMO had optico-spinal MS (OSMS; n = 3), longitudinally extensive transverse myelitis (TM) (n = 35), recurrent optic neuritis (ON) (n = 2), ON with Sjögren’s syndrome (n = 1) and TM positive for Sjögren-A(SSA) antibody (n = 1). The sensitivity and specificity of AQP4 antibodies in NMO were 70.9% and 91%, respectively. The median AQP4 antibody titer was significantly higher in patients with NMO (1:320) than in those with HR-NMO (1:100) and MS (1:50). Relapse of ON or TM was more likely in patients with AQP4 seropositive, than AQP4 seronegative, HR-NMO. Among AQP4 seropositive patients, 66.7% (36/55) had severe ON, 75.9% (41/55) had TM, and 55.6% (30/55) had spinal cord lesions longer than three segments, and there were relapses in eight of 55 patients with ON (14.8%) and 19 of 55 patients with TM (35.2%) during the 2-year follow-up. In conclusion, our study reveals that AQP4 antibody is a sensitive and specific biomarker for discrimination of NMO, classic MS, and other neurological diseases, and is particularly useful for the diagnosis of HR-NMO. AQP4 antibody-positive patients showed higher frequencies of relapse of ON or TM compared with AQP4 antibody-negative patients.     

Comorbidity,age of onset and suicidality in obsessive–compulsive disorder (OCD): An international collaboration

ObjectivesTo collate data from multiple obsessive–compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive–compulsive and related disorders.MethodsResearchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD.ResultsData from 3711 adult patients with primary OCD came from Brazil (n = 955), India (n = 802), Italy (n = 750), South Africa (n = 565), Japan (n = 322), Australia (n = 219), and Spain (n = 98). The most common current comorbid disorders were major depressive disorder (28.4%; n = 1055), obsessive–compulsive personality disorder (24.5%, n = 478), generalized anxiety disorder (19.3%, n = 716), specific phobia (19.2%, n = 714) and social phobia (18.5%, n = 686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n = 1874). OCD generally had an age of onset in late adolescence (mean = 17.9 years, SD = 1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n = 200) of patients with OCD and 9.0% (n = 314) reported a lifetime history of suicide attempt.ConclusionsIn this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.     

Transorbital neuroendoscopic surgery for the treatment of skull base lesions

Transorbital neuroendoscopic surgery (TONES) is a relatively new technique that not only allows access to the contents of the orbit but also the intracranial compartment, including the anterior cranial fossa, middle fossa and lateral cavernous sinus. In this study, we aimed to retrospectively review the largest experience to our knowledge with regards to surgical outcomes of skull base pathologies treated with a TONES procedure. Forty patients (aged 3–89 years) underwent 45 TONES procedures between the years of 2006–2013. Pathologies were cerebrospinal fluid leak repair (n = 16), traumatic fracture (n = 8), tumor (n = 11), meningoencephalocele (n = 5), hematoma (n = 1), and infection (n = 4). Three patients had a persistent complication at 3 months, including a case each of enophthalmos (unnoticed by patient), epiphora (delayed presentation at 2 months requiring dacryocystorhinostomy), and ptosis (improved at 1 year). Surgical success was achieved in all patients. Of special import, there were no cases of visual decline, diplopia, or stroke. There was no mortality. To our knowledge this is the first study and largest experience of TONES (level 4 evidence) to detail outcomes with respect to skull base pathologies. Our results indicate that TONES procedures can be performed with minimal morbidity. Further studies are needed to assess equivalency with craniotomy based approaches though this initial report is encouraging.     

Non-Wilsonian hepatolenticular degeneration: Clinical and MRI observations in four families from south India

Non-Wilsonian hepatolenticular degeneration (NWHD) is a heterogeneous neurological disorder occurring secondary to chronic acquired liver disease. Genetically determined familial NWHD is rare, poorly understood, and often mistaken for Wilson’s disease (WD). We analysed clinical and MRI profiles of NWHD patients who did not have obvious cause for acquired liver disease, such as alcohol intake or hepatitis. Six patients from four families (four males, two females, mean age: 17.0 ± standard deviation 7.9 years), presenting with chronic extrapyramidal disorder resembling WD and imaging (abdominal ultrasound/MRI) evidence of cirrhosis were studied. They lacked Kayser–Fleischer rings or biochemical and/or genetic evidence of WD. Clinical features included dystonia (n = 6), parkinsonism (n = 3), tremor (n = 1), cerebellar ataxia (n = 3), orofacial dyskinesia (n = 1), behavioural abnormalities (n = 3), and cognitive decline (n = 1). Brain MRI revealed T1-weighted hyperintensity in the pallidum (n = 6), crus cerebri (n = 4), putamen (n = 1), caudate (n = 1), thalamus (n = 1), and red nucleus (n = 1) with T2-weighted shortening in some of these regions. Additional findings included giant cisterna magna (n = 1), face of giant panda sign (n = 1) and thin corpus callosum (n = 1). Areas of “blooming” on susceptibility weighted images were noted in two patients in the caudate (n = 2) and putamen (n = 1). The finding of T1 shortening is distinct from that of WD where the majority of lesions are T1-hypointense and T2-hyperintense. Extrapallidal T1-hyperintensity is also an exceptional observation in NWHD. The MRI appearance of intense T1 shortening coupled with the lack of increased susceptibility changes suggests that the most likely mineral deposited is manganese. The association of this neurological disorder and cirrhosis of the liver in the absence of an acquired liver disease is a distinct disease entity. This syndrome may represent a disorder of manganese metabolism resulting in its toxic deposition.     

Whole-brain CT perfusion combined with CT angiography for ischemic complications following microsurgical clipping and endovascular coiling of ruptured intracranial aneurysms

Ischemic complications associated with microsurgical clipping and endovascular coiling affects the outcome of patients with intracranial aneurysms. We prospectively evaluated 58 intracranial aneurysm patients who had neurological deterioration or presented with poor grade (Hunt-Hess grades III and IV), aneurysm size >13 mm and multiple aneurysms after clipping or coiling. Thirty patients had ischemic complications (52%) as demonstrated by whole-brain CT perfusion (WB-CTP) combined with CT angiography (CTA). Half of these 30 patients had treatment-associated reduction in the diameter of the parent vessels (n = 6), ligation of the parent vessels or perforating arteries (n = 2), and unexplained or indistinguishable vascular injury (n = 7); seven of these 15 (73%) patients suffered infarction. The remaining 15 patients had disease-associated cerebral ischemia caused by generalized vasospasm (n = 6) and focal vessel vasospasm (n = 9); six of these 15 (40%) patients developed infarction. Three hemodynamic patterns of ischemic complications were found on WB-CTP, of which increased time to peak, time to delay and mean transit time associated with decreased cerebral blood flow and cerebral blood volume were the main predictors of irreversible ischemic lesions. In conclusion, WB-CTP combined with CTA can accurately determine the cause of neurological deterioration and classify ischemic complications. This combined approach may be helpful in assessing hemodynamic patterns and monitoring operative outcomes.     

Identification and measurement of cervical spinal cord atrophy in neuromyelitis optica spectrum disorders (NMOSD) and correlation with clinical characteristics and cervical spinal cord MRI data

IntroductionThe spinal cord is one of the two main targets of neuromyelitis optica (NMO). The aim of this study was to highlight cervical spinal cord atrophy in NMO patients as compared to controls and to assess correlations between atrophy and clinical characteristics and cervical spinal cord MRI data.MethodsThis prospective study investigated 15 patients with a diagnosis of NMOSD and 15 healthy controls. The whole cervical spinal cord was explored by MRI. The cross-sectional area (CSA) was estimate at every level of cup. This measurement was then averaged on the whole cervical spinal cord, providing a single measurement for every subject, denoted as mean CSA.ResultsMean CSA was 68.5 mm2 in the population of NMO patients and 72.8 mm2 in the population of healthy subjects. NMO patients had significantly smaller cervical spinal cord area than healthy controls (T test = 0.009). Cervical spinal cord atrophy was associated with clinical signs of medullary involvement (T test = 0.0006). There was a tendency toward a relation between cervical spinal cord atrophy and the Expanded Disability Status Scale (EDSS) (T test = 0.07). This correlation seems statistically significant (T test < 0.05) at the level of the upper cervical spinal cord (C2-C3)ConclusionThis study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord.     

Cerebrospinal fluid ferritin — Unspecific and unsuitable for disease monitoring

Background and purposeSubarachnoid hemorrhage is sometimes difficult to diagnose radiologically. Cerebrospinal fluid (CSF) ferritin has been proposed to be highly specific and sensitive to detect hemorrhagic central nervous system (CNS) disease. We analyzed here the specificity of CSF ferritin in a large series of various CNS diseases and the influence of serum ferritin.Materials and methodsCSF ferritin, lactate, protein and total cell count were analyzed in 141 samples: neoplastic meningitis (n = 62), subarachnoid hemorrhage (n = 20), pyogenic infection (n = 10), viral infection (n = 10), multiple sclerosis (n = 10), borreliosis (n = 5) and normal controls (n = 24). Cerebrospinal fluid ferritin was measured with a microparticle immunoassay. In addition, serum and CSF ferritin were compared in 18 samples of bacterial and neoplastic meningitis.ResultsIn CNS hemorrhage, median ferritin was 51.55 μg/L (sensitivity: 90%) after the second lumbar puncture. In neoplastic meningitis, the median CSF ferritin was 16.3 μg/L (sensitivity: 45%). Interestingly, ferritin was higher in solid tumors than that in hematological neoplasms. In 90% of pyogenic inflammation, ferritin was elevated with a median of 53.35 μg/L, while only 50% of patients with viral infection had elevated CSF ferritin. In ventricular CSF, median ferritin was 163 μg/L, but only 20.6 μg/L in lumbar CSF. Ferritin was normal in multiple sclerosis and borreliosis.ConclusionsFerritin was elevated not only in hemorrhagic disease, but also in neoplastic and infectious meningitis. Ferritin was not a reliable marker of the course of disease. The influence of serum ferritin on CSF ferritin is negligible. We conclude that elevated CSF ferritin reliably, but unspecifically indicates severe CNS disease.     

Extreme lateral interbody fusion for the treatment of adult degenerative scoliosis

Extreme lateral interbody fusion (XLIF; NuVasive Inc., San Diego, CA, USA) is a minimally invasive lateral transpsoas approach to the thoracolumbar spine. Though the procedure is rapidly increasing in popularity, limited data is available regarding its use in deformity surgery. We aimed to evaluate radiographic correction using XLIF in adults with degenerative lumbar scoliosis. Thirty consecutive patients were followed for an average of 14.3 months. Interbody fusion was completed using the XLIF technique with supplemental posterior instrumentation. Plain radiographs were obtained on all patients preoperatively, postoperatively, and at most recent follow-up. Plain radiographic measurements of coronal Cobb angle, apical vertebral translation, segmental lordosis, global lordosis, disc height, neuroforaminal height and neuroforaminal width were made at each time point. CT scans were obtained for all patients 1 year after surgery to evaluate for fusion. There was significant improvement in multiple radiographic parameters from preoperative to postoperative. Cobb angle corrected 72.3%, apical vertebral translation corrected 59.7%, neuroforaminal height increased 80.3%, neuroforaminal width increased 7.4%, and disc height increased 116.7%. Segmental lordosis at L4–L5 increased 14.1% and global lordosis increased 11.5%. There was no significant loss of correction from postoperative to most recent follow-up. There was an 11.8% pseudoarthrosis rate at levels treated with XLIF. Complications included lateral incisional hernia (n = 1), rupture of anterior longitudinal ligament (n = 2), wound breakdown (n = 2), cardiac instability (n = 1), pedicle fracture (n = 1), and nonunion requiring revision (n = 1). XLIF significantly improves coronal plane deformity in patients with adult degenerative scoliosis. XLIF has the ability to correct sagittal plane deformity, although it is most effective at lower lumbar levels.     

Tyrosine metabolism during interferon-alpha administration: Association with fatigue and CSF dopamine concentrations

Chronic exposure to interferon (IFN)-alpha, an innate immune cytokine, produces high rates of behavioral disturbances, including depression and fatigue. These effects may be mediated by the actions of IFN-alpha on dopamine (DA) metabolism in the basal ganglia. Diminished conversion of phenylalanine (Phen) to tyrosine (Tyr), the primary amino acid precursor of DA, has been associated with inflammation, and may reflect decreased activity of the enzyme phenylalanine-hydroxylase (PAH). This study investigated the peripheral Phen/Tyr ratio in relation to cerebrospinal fluid (CSF) concentrations of DA and its metabolites in subjects treated with IFN-alpha plus ribavirin for hepatitis C and controls awaiting IFN-alpha therapy. Plasma Phen/Tyr ratios were significantly increased in IFN-alpha-treated subjects (n = 25) compared to controls (n = 9), and were negatively correlated with CSF DA (r = −0.59, df = 15, p < 0.05) and its metabolite, homovanillic acid (r = −0.67, df = 15, p < 0.01), and positively correlated with fatigue (r = 0.44, df = 23, p < .05) in IFN-alpha-treated patients but not controls. Given the role of tetrahydrobiopterin (BH4) in the PAH conversion of Phen to Tyr, CSF concentrations of BH4 and its inactive oxidized form, dihydrobiopterin (BH2), were examined along with CSF interleukin (IL)-6 in a subset of patients. BH2 concentrations were significantly increased in IFN-alpha-treated patients (n = 12) compared to controls (n = 7), and decreased CSF BH4 concentrations correlated with increased CSF IL-6 (r = −0.57, df = 12, p < 0.05). These results indicate that IFN-alpha is associated with decreased peripheral conversion of Phen to Tyr, which in turn is associated with reduced DA in the brain as well as fatigue. These alterations may be related to oxidation of BH4 secondary to IFN-alpha-induced activation of a CNS inflammatory response.     

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter,observational study

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400 mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9–87 years) enrolled in the study and were treated with ESL at either 400 mg/day (3.4% patients), 800 mg/day (61% patients), 1200 mg/day (27.1% patients) or 1600 mg/day (8.5% patients). At 3 months, 82.0% (n = 72) of patients achieved a ≥ 50% reduction in seizure frequency, compared to 79.7% (n = 67) of patients at 6 months and 83.0% (n = 49) at 12 months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n = 27), 69.6% (n = 29), and 72.7% (n = 16) at 3, 6, and 12 months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n = 9), somnolence (n = 3), mild hyponatremia (n = 3), headache (n = 1), hypertriglyceridemia (n = 1), and allergic reaction (n = 1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.     

Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample

ObjectiveThe literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6), interleukin-8 (IL-8) and depression in a population-based sample of older women who were followed for 17 years.Methods86 dementia-free women aged 70–84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992–3. CSF IL-6 and CSF IL-8 were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria.ResultsAt baseline, women with ongoing major (n = 10) or minor depression (n = 9) had higher levels of CSF IL-6 (p = 0.008) and CSF IL-8 (p = 0.007) compared with those without depression (n = 67). Higher CSF IL-8 was related to higher MADRS score (p = 0.003). New cases of depression were observed in 9 women during follow-ups. No associations between CSF cytokine levels and future depression could be shown in women without depression at baseline.ConclusionHigher levels of CSF IL-6 and IL-8 were associated with current depression in this population-based sample. CSF IL-6 and CSF IL-8 may play a role in depression in late life.     

Factors affecting surgical outcome of endoscopic third ventriculostomy in congenital hydrocephalus

Endoscopic third ventriculostomy (ETV) is an accepted modality of treatment for obstructive hydrocephalus, with good results in adult patients. However in the pediatric age group results vary from poor to similar to the adult population. This study evaluates the outcome of ETV in congenital hydrocephalus of both early and delayed presentation, and investigates factors that determine the outcome. Patients with congenital hydrocephalus who underwent ETV between January 2006 and December 2011 were retrospectively analyzed. Any conditions potentially influencing the need for redo surgery (persistent cerebrospinal fluid [CSF] leak not responding to local measures, tense fontanelle, increased ventricular size, recurrence of symptoms or radiological evidence of failure) were analyzed. A total of 102 patients with a mean age of 7.45 years were included. Presenting features were increasing head circumference and delayed milestones. Ninety-eight patients had triventricular hydrocephalus due to aqueductal stenosis. Procedures performed were ETV only (n = 74), ETV with aqueductoplasty (n = 22), ETV with cystoventriculostomy (n = 2) and aqueductoplasty only (n = 2). Failure of ETV occurred in 11 patients and all were managed with a ventriculoperitoneal shunt. CSF leak in the perioperative period was the only factor that was significantly associated with failure of ETV. ETV is a safe procedure with a good success rate and can be offered to children with aqueductal stenosis. There is a higher chance of failure if there is a CSF leak in the early or late postoperative period.     

Exercise-induced changes of cerebrospinal fluid vascular endothelial growth factor in adult chronic hydrocephalus patients

Vascular endothelial growth factor (VEGF) is a growth factor demonstrated to be a key factor in cerebral angiogenesis and neurogenesis. It has been considered a critical component in hippocampus neurogenesis and memory formation and has been observed to increase in the rat hippocampus after exercise. We previously found increased VEGF levels in experimental chronic hydrocephalus in several brain areas and cerebrospinal fluid (CSF), suggesting a role in the adaption to chronic hypoxia. Here we investigate the ability of moderate exercise to increase CSF-VEGF levels in adult chronic hydrocephalus patients. Lumbar CSF samples were collected from 17 normal pressure hydrocephalus patients. During CSF collection, 11 patients (exercise group) underwent a standard in-room occupational therapy session; six patients (no-exercise group) did not undergo a physical therapy session. CSF-VEGF levels were evaluated for increase related to exercise and the clinical response to CSF drainage. CSF-VEGF levels in the exercise group demonstrated significant increases 1–3 hours post-exercise compared with the levels 1–2 hours pre-exercise (p = 0.04), and also showed significantly higher levels than the no-exercise groups (p = 0.03). The post-exercise CSF-VEGF level in the group that did not clinically improve was significantly higher than both their own pre-exercise level (p = 0.02) and that seen in the clinically improving group (p = 0.05) after exercise. We conclude that CSF-VEGF levels can increase after moderate exercise even in elderly hydrocephalus patients. This suggests that a potential benefit of exercise, especially in CSF drainage non-improved patients, may exist via a central VEGF mechanism.     

Fatigue in primary Sjögren’s syndrome – A link to sickness behaviour in animals?

Interleukin-1β (IL-1β) is involved in the regulation of sickness behaviour in response to infection and inflammation in animals. Human fatigue can be considered an element of sickness behaviour and is a prominent and often disabling phenomenon in autoimmune diseases such as primary Sjögren’s syndrome (PSS). The role of the IL-1 system in the fatigue of patients with PSS was explored.A cerebrospinal fluid (CSF) analysis of IL-1β, IL-1Ra, and IL-1sRII was performed in 54 PSS patients and 53 control subjects. Fatigue was evaluated in the patients using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS); mood was evaluated using the Beck Depression Inventory (BDI).There were higher CSF levels of IL-1Ra pg/mL in PSS patients vs. controls (median 38.4: range 15.4–81.7 vs. 33.7: 7.3–163.1, p = 0.026). Fatigue VAS scores were associated with increasing CSF levels of IL-1Ra in PSS patients (R² = 0.11, p = 0.015). In a subgroup analysis of the non-depressed PSS patients (N = 37; 69%), the association between VAS scores and IL-1Ra was even stronger (R² = 0.20, p = 0.006). The positive association between VAS scores and IL-1Ra remained significant in a multiple regression analysis adjusting for age and BDI scores.Increased levels of IL-1Ra in the CSF are associated with increasing fatigue in PSS patients, indicating that the activated IL-1 system is a possible biological factor associated with fatigue.     

Finger tapping analysis in patients with Parkinson’s disease and atypical parkinsonism

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson’s disease (PD), progressive supranuclear palsy–Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n = 13), PSP-R (n = 15), and MSA-P (n = 14) patients and matched healthy controls (HC; n = 14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of −0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (−0.21°/cycle, p = 0.032), and particularly from PD (−0.56°/cycle, p = 0.001), and MSA-P patients (−1.48°/cycle, p = 0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (p_msa-pd = 0.726, p_msa-psp = 0.363, p_psp-pd = 0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.