Patients Underwent Lumbar Puncture Research Articles

Discordant CSF/plasma HIV-1 RNA in patients with unexplained low-level viraemia.

The central nervous system has been proposed as a sanctuary site where HIV can escape antiretroviral control and develop drug resistance. HIV-1 RNA can be at higher levels in CSF than plasma, termed CSF/plasma discordance. We aimed to examine whether discordance in CSF is associated with low level viraemia (LLV) in blood. In this MRC-funded multicentre study, we prospectively recruited patients with LLV, defined as one or more episode of unexplained plasma HIV-1 RNA within 12 months, and undertook CSF examination. Separately, we prospectively collected CSF from patients undergoing lumbar puncture for a clinical indication. Patients with durable suppression of viraemia and no evidence of CNS infection were identified as controls from this group. Factors associated with CSF/plasma HIV-1 discordance overall were examined. One hundred fifty-three patients were recruited across 13 sites; 40 with LLV and 113 undergoing clinical lumbar puncture. Seven of the 40 (18 %) patients with LLV had CSF/plasma discordance, which was significantly more than 0/43 (0 %) with durable suppression in blood from the clinical group (p = 0.005). Resistance associated mutations were shown in six CSF samples from discordant patients with LLV (one had insufficient sample for testing), which affected antiretroviral therapy at sampling in five. Overall discordance was present in 20/153 (13 %) and was associated with nadir CD4 but not antiretroviral concentrations in plasma or CSF. CSF/plasma discordance is observed in patients with LLV and is associated with antiretroviral resistance associated mutations in CSF. The implications for clinical practice require further investigation.

Intravenous Fluid Bolus Prior to Neonatal and Infant Lumbar Puncture: A Sonographic Assessment of the Subarachnoid Space After Intravenous Fluid Administration.

Neonatal and infant lumbar puncture is a commonly performed procedure in emergency departments, yet traumatic and unsuccessful lumbar punctures occur 30% to 50% of the time. Dehydration may be a risk factor for unsuccessful lumbar punctures, but to our knowledge, no studies have investigated the use of intravenous (IV) fluid bolus prior to lumbar puncture. To investigate the association of IV fluid bolus administration with the sonographic measure of the neonatal and infant lumbar subarachnoid space. We hypothesized that IV fluids would increase subarachnoid space size. Prospective observational study conducted from August 2012 to April 2015.The study took place at the emergency department of the Children's Hospital Los Angeles, an urban pediatric emergency department with an annual census of 76,000 visits.A convenience sample of patients aged 0 to 3 months were enrolled if they had a clinical presentation consistent with pyloric stenosis. This population was used as a proxy because they are similar in age to patients undergoing lumbar puncture for evaluation of neonatal fever and are routinely given IV fluids for dehydration. Patients with a sonographic diagnosis of pyloric stenosis underwent additional ultrasonography evaluation to determine the size of the subarachnoid space before and after IV fluids. Primary outcomes included the difference in the size of the subarachnoid space in millimeters squared before and 1 hour after administration of an IV fluid bolus in the emergency department. Interobserver consistency for the subarachnoid space measurement between attending radiologists was measured using intraclass correlation coefficient. The Wilcoxon signed-rank test was used to examine changes in subarachnoid space measurements (millimeters squared). The study sample consisted of 40 patients with a mean (SD) age of 37 (11.3) days (range, 15-71 days). The mean (SD) size of the subarachnoid space before and 1 hour after IV fluid bolus was 37.8 (11.1) mm(2) and 36.9 (11.2) mm(2) respectively (P = .42). The intraclass correlation coefficient ranged from 0.96 to 0.99 (95% CI, 0.90-0.99). Intravenous fluid boluses were not associated with a significant increase in the sonographic measure of the neonatal and infant subarachnoid space.

Lumbar Myelography in a Crab-Eating Raccoon (Procyon cancrivorus)

Background: The Crab-eating raccoon (Procyon cancrivorus) is a nocturnal mammal and lives in savannah, but loss of their natural habitat makes increase cases of traffic accidents on the roads. A growing number of wildlife are treated in veterinary hospitals, but we have some limitation about the correct interpretation of the diagnostic test, specially because, even the tests were not described. Myelography is a radiographic technique indicated for compressive lesions of the spinal cord that are not seen on plain radiographs. The present report aims to describe, for the first time, a lumbar myelogram performed in a paraplegic crab-eating raccoon after it suffer a traffic trauma.Case: A free living adult, 8-kg, female raccoon was presenting acute paraplegia and swelling in the region of the left humerus was referred at veterinary hospital. The patient was alert and aggressive, good body score and no signs of active bleeding. The animal temper did not allow approaching it; therefore, physical and neurological examinations were not feasible. The raccoon was tranquilized (1.6 mL of nilperidol® intramuscular), anesthetized (propofol, dose-effect intra­venous) and tracheal intubation to provide oxygen and the patient was monitored continuously, followed by referred for radiology service. The simple radiograph showed a complete transverse fracture in the humerus and compression fracture of the twelfth thoracic vertebra (T12), being then indicated the myelographic examination to assess the extent of spinal cord compression. The lumbar region was surgical antisepsis prepared. After being properly positioned in lateral decubitus with moderate cranial flexion of the trunk, the patient underwent lumbar puncture by inserting a spinal needle between the 5th and 6th intervertebral lumbar spaces. The spinal needle was introduced slightly caudolaterally to the spinous process of the 6th lumbar vertebra and cranioventrally directed at an angle of 45º. Then, the needle was pierced through the ligamentum flavum and the dura mater while, concomitantly, we observed the tail moving and the cerebrospinal fluid (CSF) output while the contrast was injected. The contrast iohexol (300 mg/mL) was used at a dose of 0.25 mL/kg. Immediately after the slow injection of contrast (approximately 3 min), radiographs were taken in the latero-lateral and ventrodorsal projections to identify the location of the spinal cord disorder. The extension degree of the lesion was evidenced by the reduction of the contrast column width at the location of instability. The patient was referred for surgical decompression and stabilization.Discussion: In cases where paraplegia results from trauma, spinal radiography and myelography are important means to confirm the diagnosis, specially the extent of the compression and prognosis. There are certain risks inherent in the myelography procedure as arrhythmias and bradycardia during collection, transient apnea during contrast injection and seizures during recovery. Furthermore, deteriorating neurological signs, emesis, urinary retention and hyperthermia are other possible complications. Most of these complications are seen predominantly during cervical myelography compared to lumbar puncture because in the first exam, the contrast hardly reaches the brain and there is no risk of iatrogenic injury to the medulla oblongata. To minimize the neurotoxic effects, the ideal contrast should be radiopaque, water soluble, mis­cible with the cerebrospinal fluid (CSF), nontoxic and removed from the CSF by physiological processes. Iohexol contrast was used effectively, without neurotoxicity upon clinical evaluation while the volume used was sufficient to determine the injury site. The reported case demonstrated the possibility of performing lumbar myelography on Procyon cancrivorus effectively without significant complications or difficulties.Keywords: wildlife, neurology, myelographic examination, Procyon cancrivoru.

An algorithmic approach to the management of unrecognized hydrocephalus in pediatric candidates for intrathecal baclofen pump implantation.

Background:Complications of intrathecal baclofen (ITB) pump implantation for treatment of pediatric patients with spasticity and dystonia associated with cerebral palsy remain unacceptably high. To address the concern that some patients may have underlying arrested hydrocephalus, which is difficult to detect clinically because of a low baseline level of neurological function, and may contribute to the high rates of postoperative cerebrospinal fluid leak, wound breakdown, and infection associated with ITB pump implantation, the authors implemented a standardized protocol including mandatory cranial imaging and assessment of intracranial pressure (ICP) by lumbar puncture prior to ITB pump implantation.Methods:A retrospective case series of patients considered for ITB pump implantation between September 2012 and October 2014 at Seattle Children's Hospital is presented. All patients underwent lumbar puncture under general anesthesia prior to ITB pump implantation and, if the opening pressure was greater than 21 cmH2O, ITB pump implantation was aborted and alternative management options were presented to the patient's family.Results:Eighteen patients were treated during the study time period. Eight patients (44.4%) who had ICPs in excess of 21 cmH2O on initial LP were identified. Eleven patients (61.1%) ultimately underwent ITB pump implantation (9/10 in the “normal ICP” group and 2/8 in the “elevated ICP” group following ventriculoperitoneal shunt placement), without any postoperative complications.Conclusions:Given the potentially high rate of elevated ICP and arrested hydrocephalus, the authors advocate pre-implantation assessment of ICP under controlled conditions and a thoughtful consideration of the neurosurgical management options for patients with elevated ICP.

Ultrasound evaluation of internal jugular valve incompetence (IJVI) in Egyptian patients with idiopathic intracranial hypertension (IIH)

BackgroundIdiopathic intracranial hypertension (IIH) is a clinical syndrome with no identified causative factor. Internal jugular valve incompetence (IJVI) has been linked to many neurological disorders such as idiopathic intracranial hypertension (IIH), transient global amnesia and cough-induced headache. Intact valves prevent efficiently retrograde flow into the internal jugular vein. AimThe aim of this study is to evaluate the competence of the jugular vein valves and its relationship to age, BMI, opening CSF pressure and MRV findings in IIH patients. Subjects and methodsTwenty-five Egyptian female patients diagnosed with IIH according to the modified Dandy criteria, and 24 female controls, matched for age and BMI, were included and examined using color-coded duplex for IJVI during the Valsalva maneuver. The patients underwent lumbar puncture to measure the opening pressure, MRV, ophthalmic examination and laboratory work-up. ResultsThere was no statistically significant difference in the proportion of IJVI among the patients and controls (P=0.7). There was a statistically significant increase in the opening pressure and proportion of MRV abnormalities in the patients with IJVI compared to the patients without IJVI (P=0.03 and 0.007, respectively), but there were no statistically significant difference with regard to age, BMI, grade of papilledema and perimetry findings. ConclusionThis study showed that there is no relationship between IJVI and IIH; thus, IJVI would be a rather normal finding. Further studies are recommended to confirm or rule out a possible relationship.

Changes of laboratory indices in serum and cerebrospinal fluid for children retinoblastoma before and after chemotherapy

Objective To analyze the changes of laboratory indices in serum and cerebrospinal fluid(CSF)for children retinoblastoma(RB)before and after chemotherapy between central nervous system (CNS) metastasis group and extraocular stage group, and to conclude the clinical significance. Methods From September 2005 to December 2013, 11 cases were collected in Beijing Tongren Hospital who were diagnosed as CNS metastasis and were assorted into CNS metastasis group.According to age, gender and eye difference, 11 cases were chosen for the extraocular stage group.Twenty-two cases were given 6 cycles of chemotherapy.The chemotherapy protocol was Carboplatin + Teniposide + Vincristine(CTV) or Carboplatin + Etoposide + Vincristine(CEV). In each chemotherapy cycle all patients underwent lumbar puncture and intrathecal injection therapy.Serum levels of neuron specific enolase (NSE), serum lactate dehydrogenase (LDH) and CSF levels of NSE, quantitative protein and white blood cell count of the two groups were monitored before initiating chemotherapy and after the third and sixth cycles of chemotherapy.Multi factor variance analysis of the data was compared between the two groups in the dynamic changes of laboratory indices before and after chemotherapy using repeated measurements. Results The serum NSE levels of CNS metastasis group before initiating chemotherapy and after the 6th cycle of chemotherapy were (120.19±105.19) μg/L and (39.07±24.10) μg/L, respectively.The serum NSE levels of extraocular stage group before initiating chemotherapy and after the 6th cycle of chemotherapy were (29.03±11.94) μg/L and (21.03±5.01) μg/L, respectively.Serum NSE levels of the two groups showed significant changes before and after chemotherapy (F=7.115, P=0.000). Serum NSE level of CNS metastasis group was significantly higher than that of the extraocular stage group(F=41.500, P=0.007). Serum LDH levels of the two groups showed no statistically significant changes before and after chemotherapy (F=0.892, P=0.525). The CSF-NSE level of CNS metastasis group was significantly higher than that of extraocular stage group(F=15.706, P=0.001). CSF quantitative protein level of the CNS metastasis group was significantly higher than that of extraocular stage group(F=15.228, P=0.001). CSF white blood cell count of the CNS metastasis group were significantly higher than that of extraocular stage group(F=5.514, P=0.003). Conclusions Serum NSE level can be used as a laboratory indicator for monitoring CNS metastasis stage and extraocular stage of RB.The CSF-NSE values can be used as a diagnostic tool for CNS metastasis and monitoring of disease progression.CSF quantitative protein and white blood cell count can be used as auxiliary laboratory index for CNS metastasis diagnosis.Serum LDH cannot be used as a valuable laboratory index for diagnosis of CNS metastasis cases and extraocular cases. Key words: Retinoblastoma; Neuron specific enolase; Lactate dehydrogenase; Cerebrospinal fluid

CSF pressure, papilledema grade, and response to acetazolamide in the Idiopathic Intracranial Hypertension Treatment Trial.

Previous reports suggest an association between the degree of optic nerve head edema and CSF pressure (CSFp) in idiopathic intracranial hypertension (IIH). We hypothesized that CSFp would be associated with Frisén papilledema grade (FPG) and other clinical features, and that FPG would modify the CSFp response to acetazolamide in participants in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). In the IIHTT, eligible patients underwent lumbar puncture (LP) prior to enrollment and were randomly assigned to one of two treatment groups: acetazolamide plus supervised diet or placebo plus supervised diet. Trial eligibility required baseline CSFp ≥250 mm H2O or ≥200 mm H2O with compelling clinical or imaging IIH findings. Associations between CSFp and FPG and other clinical features were examined at baseline. The effect of acetazolamide on 6-month change in CSFp was examined in those with low FPG (grades I-III) and those with high FPG (grades IV-V) at baseline. All 165 enrolled subjects had a baseline LP and 85 had an LP at 6 months. There was an association between CSFp and FPG at baseline: CSFp was more elevated in subjects with high FPG (378 ± 90 mm H2O, n = 50) than in subjects with low FPG (331 ± 77, n = 115, p = 0.002). At 6 months, acetazolamide had a similar effect on CSFp in subjects with high FPG (-79.9 mm H2O) and in subjects with low FPG (-50.9 mm H2O, p = 0.50). We found a modest association between CSFp and FPG. Acetazolamide had a beneficial effect on CSFp regardless of baseline FPG.

P93 – 2953: Identification of a new mutation of the SCL1A gene in a patient with GLUT1-DS

Objective Diagnostic assessment of a boy of 13 years old. From the age of 16 months, he has showed an isolated oculomotor disorder associated with a delay in acquisition of psychomotor milestones. Furthermore, at 4 years old, he presented absence-like seizures, for whom he has been favourably treated with valproic acid. After 9 years of wellness, when antiepileptic drug was stopped, an effort-related paroxysmal myoclonic dystonia appeared, involving mostly lower limbs. Such episodes have rapidly increased in frequency, becoming truly debilitating for the patient. Methods Suspecting a deficit of the enzyme GLUT1, the patient underwent lumbar puncture, video-EEG and molecular genetic analysis. Physical-chemical analysis of CSF demonstrated a glycorrhachia of 45 mg/dL, lactate at the lower limit of the normal range and a CSF/serum glucose ratio of 0.52. Video-EEG excluded epileptic paroxysms. Results The molecular investigation revealed a point mutation not previously described in literature (c.1199G>A; exon 9 – gene SLC2A1); this mutation was absent in parental alleles and thus it was originated de novo. Conclusion After diagnosis, the patient restarted therapy with valproic acid and began to follow strictly ketogenic diet, getting a complete and persistent clinical remission. In conclusion, this report of a GLUT1-DS case is characterized by an unusual presentation and the description of a new causative mutation. More interestingly, it proves the importance of CSF analysis to potentially reveal treatable diseases in children with undiagnosed movement disorders.

High-dose oral amoxicillin plus probenecid is highly effective for syphilis in patients with HIV infection.

Intramuscular benzathine penicillin G (BPG) is widely used for the treatment of syphilis. However, BPG is not available in some countries. This study examined the effectiveness and safety of high-dose oral amoxicillin plus probenecid for the treatment of syphilis in patients with human immunodeficiency virus type 1 (HIV-1). This retrospective observational study included 286 HIV-infected male patients with syphilis (median age, 36 years; median CD4 count, 389 cells/µL) who were treated with oral amoxicillin 3 g plus probenecid. Syphilis was diagnosed by both serum rapid plasma reagin (RPR) titers ≥8 and positive Treponema pallidum hemagglutination test. Patients with neurosyphilis diagnosed by cerebrospinal fluid examination were excluded. Successful treatment was defined as a at least 4-fold decrement in RPR titer. The overall treatment efficacy was 95.5% (95% confidence interval [CI], 92.4%-97.7%; 273/286 patients), and efficacy for primary, secondary, early latent, late latent, and unknown duration syphilis was 93.8% (95% CI, 68.1%-99.8%; 15/16), 97.3% (95% CI, 92.9%-99.2%; 142/146), 100% (95% CI, 90.5%-100%; 37/37), 85.7% (95% CI, 58.6%-96.4%; 18/21), and 92.4% (95% CI, 81.9%-97.3%; 61/66), respectively. Treatment duration was mostly 14-16 days (49.7%) or 28-30 days (34.3%), with efficacy of 94.4% (134/142) and 95.9% (94/98), respectively; 96.3% of successfully treated patients achieved a ≥4-fold decrement in RPR titer within 12 months. Adverse events were noted in 28 (9.8%) patients, and 25 of these (89.3%) were successfully treated. Only 6% of patients underwent lumbar puncture. The combination of oral amoxicillin 3 g plus probenecid was highly effective and tolerable for the treatment of syphilis in patients with HIV-1 infection.

Investigating the Causes of Febrile Encephalopathy in Elderly Patients Admitted to Imam Reza Hospital in Mashhad during the 2013 to 2014

Background: Encephalopathy is a non-specific clinical syndrome, which if accompanied or followed by fever, its broad range of differential diagnosis will be restricted. As elderly patients with encephalopathy present with nonspecific manifestations, the recognition of causes are important for clinicians to manage the disease with more accuracy. This study evaluated the causes of encephalopathy following febrile illness in elderly adults admitted to Imam Reza hospital of Mashhad, Iran. Methods and materials: This prospective cohort study was carried out during January 2013 to January 2014. An application check-list was designed based on the objects of the study and was filled for all admitted patients. Checklist contained data including age, sex, and disease outcome, duration of hospitalization, background disease, and season of admission, performing or not performing brain imaging and lumbar puncture; and the final diagnosis of febrile encephalopathy. Results: The age of all 100 participants were 65 years and over consisting of 39 female and 61 male. Of them, only 34 patients underwent lumbar puncture, among them the cerebrospinal fluid (CSF) analysis was abnormal in 29.4%. Infectious causes were responsible for febrile encephalopathy in 94 patients, of which 84% had an extracranial infection and neuro-infectious process was detected in 10%. Discussion: Current study presented extra-cranial infections as the leading cause of febrile encephalopathy in elderly patients. So, it should be considered as an important origin whenever an older patient presents with fever and altered mental status.

Intracranial pressure modulates distortion product otoacoustic emissions: a proof-of-principle study.

There is an important need to develop a noninvasive method for assessing intracranial pressure (ICP). We report a novel approach for monitoring ICP using cochlear-derived distortion product otoacoustic emissions (DPOAEs), which are affected by ICP. We hypothesized that changes in ICP may be reflected by altered DPOAE responses via an associated change in perilymphatic pressure. We measured the ICP and DPOAEs (magnitude and phase angle) during opening and closing in 20 patients undergoing lumbar puncture. We collected data on 18 patients and grouped them based on small (<4 mm Hg), medium (5-11 mm Hg), or large (≥15 mm Hg) ICP changes. A permutation test was applied in each group to determine whether changes in DPOAEs differed from zero when ICP changed. We report significant changes in the DPOAE magnitudes and angles, respectively, for the group with the largest ICP changes and no changes for the group with the smallest changes; the group with medium changes had variable DPOAE changes. We report, for the first time, systematic changes in DPOAE magnitudes and phase in response to acute ICP changes. Future studies are warranted to further develop this new approach. DPOAE, distortion product otoacoustic emissionICP, intracranial pressureIIH, idiopathic intracranial hypertensionLP, lumbar punctureTBI, traumatic brain injury.

The Role and Reliability of Rapid Bedside Diagnostic Test in Early Diagnosis and Treatment of Bacterial Meningitis

To evaluate the role and reliability of rapid bedside diagnostic test in early diagnosis and treatment of bacterial meningitis in children using reagent strips. This prospective, single blinded study was conducted in the Department of Pediatrics of VMMC & Safdarjung Hospital, New Delhi in collaboration with the Department of Microbiology of VMMC & Safdarjung Hospital, New Delhi, over a period of 15 mo (August 2009 to Nov 2010). Seventy-five children aged 3 mo to 12 y admitted in the pediatric ward with suspected diagnosis of acute meningitis were included. All enroled patients underwent lumbar puncture. CSF samples were taken and divided in 2 parts for laboratory evaluation and rapid strip analysis. The sensitivity, specificity, positive predictive value and the negative predictive values of the reagent strips for the diagnosis of bacterial meningitis were calculated. Accuracy of the reagent strips was established using kappa statistics. Latex agglutination for antigen detection and microbiological culture were also done. Highly significant association was observed between CSF examination in routine laboratory method and dipstick method. The number of laboratory values that correlated were- for cells 71(94.63%), for protein 68 (90.67%), for glucose 68(90.67%) out of total 75 cases. The sensitivity and specificity of reagent strip in diagnosing acute bacterial meningitis were 96.7% and 97.8% respectively. The positive predictive and negative predictive values of reagent strip in diagnosing acute bacterial meningitis were 96.7% and 97.8% respectively. Staphylococcus aureus was found to be the most common organism isolated (50%). Thus reagent strip analysis is a very rapid, reliable and effective method for diagnosis of acute bacterial meningitis in children. Staphylococcus aureus was the most common organism isolated.

Central Nervous System Leukemia in Acute Myeloid Leukemia

Central nervous system leukemia (CNSL) is less common in patients with acute myeloid leukemia (AML) compared to patients with acute lymphoblastic leukemia. CNSL in AML patients is rare with an incidence less than 5%. Before high dose cytarabine was incorporated into induction and consolidation regimens the incidence was higher, approximately 20%. Because of the low incidence of CNSL in AML routine evaluation (lumbar puncture with cerebrospinal fluid analysis) in patients with no CNS symptoms is not indicated at diagnosis or relapse. Patients with acute myelomonocytic leukemia, high risk or relapsed acute promyelocytic leukemia or AML with inversion 16 or chromosome 11 abnormalities may have a higher risk of CNSL. High white blood cell count at diagnosis, elevated LDH and age less than 2 years of age may also increase risk of CNSL. This study was undertaken to evaluate the incidence of CNSL in patients with newly diagnosed and relapsed AML. 298 adult patients with AML were identified through the Mayo Clinic Arizona Cancer Registry between January 2002 and February 2012. 270 had records available for retrospective review. Data on AML status (newly diagnosed/relapsed disease), cytogenetics, molecular markers, white blood count at diagnosis and lumbar puncture results was collected. 9 (4%) patients underwent lumbar puncture. 8 patients had CNS symptoms. CNS evaluation in the asymptomatic patient was performed because of high white blood cell count and myelomonocytic AML at diagnosis. 6 (67%) of the patients who underwent lumbar puncture were found to have CNSL. Of the patients with CNSL all were symptomatic, 4 had relapsed or refractory AML (1 post allogeneic hematopoietic stem cell transplant (HCT)) and 2 had initial diagnosis of AML. All patients with CNS leukemia had myelomonocytic AML. No trend in cytogenetic subtype was noted. Most patients did not have white blood count at diagnosis or molecular markers available for evaluation. AML can be a difficult disease to cure. Patients with CNSL have worse outcome and need altered treatment regimens. CNSL occurring after HCT has an even more dismal prognosis. Currently there is no indication to evaluate for CNSL in asymptomatic patients either at diagnosis, relapse or pre HCT. This small review is notable because all patients with CNSL had myelomonocytic AML. It has been suggested previously that these patients are at higher risk for CNSL. Perhaps the risk for CNSL in those with myelomonocytic AML has a higher incidence than previously reported and this patient population should have routine evaluation of the CNS. Should asymptomatic patients with myelomonocytic AML undergo lumbar puncture at initial diagnosis, relapse or pre HCT? Would prophylactic administration of intrathecal chemotherapy benefit this population? Further prospective study of the incidence of CNSL in patients with AML would be beneficial.

How often is thunderclap headache caused by the reversible cerebral vasoconstriction syndrome?

Thunderclap headache (TCH) has a broad differential diagnosis that includes the reversible cerebral vasoconstriction syndrome (RCVS). It is believed to be caused by a dysregulation of vascular tone, which leads to reversible and segmental vasoconstriction and may cause permanent neurological deficits. One of the remaining mysteries is the incidence of the syndrome in a general hospital setting. We recruited consecutive patients with TCH without evidence of aneurysmal subarachnoid hemorrhage on immediate computed tomography-scanning from the emergency room in a period of 12 months. Only those patients with an acute and severe onset of the pain were recruited; the peak of the pain had to be reached in less than 1 minute (verbal analog scale >8/10), and the minimum duration of the pain had to be 6 hours. All patients underwent lumbar puncture, magnetic resonance angiography, and serial transcranial Doppler sonography. Thirty-four patients fulfilled the inclusion criteria; 3 of those were diagnosed with the RCVS (8.8%; 95%confidence interval 3-23). We found the incidence of RCVS to be 8.8% (95% confidence interval 3-23) (3 patients) in patients presenting with TCH without evidence for severe illness. We believe that RCVS is an under recognized condition, and there fore additional imaging should be performed in every patient with TCH.

Jolt accentuation of headache and other clinical signs: poor predictors of meningitis in adults

Jolt accentuation or exacerbation of a baseline headache with horizontal rotation of the neck is a physical finding believed to assess for meningeal irritation. We conducted a prospective observational study of neurologically intact emergency department (ED) patients undergoing lumbar puncture in 2 inner city academic EDs to validate the sensitivity and specificity of jolt accentuation and to assess the sensitivity and specificity of Kernig sign, Brudzinski sign, and nuchal rigidity, in predicting cerebrospinal fluid (CSF) pleocytosis in individuals being assessed for meningitis. Adult patients 18 years and older undergoing lumbar puncture between 2006 and 2009 were approached for consent. Exclusions included inability to consent and altered mental status. Physicians were asked to answer a questionnaire of physical examination findings before receiving CSF results. The primary outcome was the presence or absence of pleocytosis, defined as greater than or equal to 5 cells/high-power field in the fourth CSF tube. We calculated descriptive statistics and tests of diagnostic accuracy. A total of 230 patients consented for participation and had CSF white blood cell counts recorded. Forty-seven individuals (20%) had pleocytosis. A total of 197 patients had headache and were, hence, eligible for jolt accentuation assessment. For pleocytosis, the sensitivity of jolt accentuation was 21%, Kernig sign was 2%, Brudzinski sign was 2%, and nuchal rigidity was 13%. The specificity of jolt accentuation was 82%, Kernig sign was 97%, Brudzinski sign was 98%, and nuchal rigidity was 80%. Jolt accentuation in our cohort was poorly predictive of pleocytosis and insensitive. The presence of Kernig sign, Brudzinski sign, or nuchal rigidity has moderate positive but no negative predictive value for pleocytosis.

The Clinical, Histopathological and Imaging Methods Characteristics of Non- Hodgkin Lymphomas in Patients with Brain Involvement

The Non- Hodgkin-lymphoma (NHL) brain infiltration carries a poor prognosis. Because of relatively rare incidence, we decided to share our experience. Retrospective analysis of patients with NHL brain infiltration dia-gnosed in 2001- 2011 at our university hospital. Twenty -seven patients with median age of 61 (range 42- 82) years were analyzed. The primary diffuse large cell B cell lymphoma of CNS was defined in 22/ 27 (81%) patients, in the others systemic NHL was present. Median positivity of the proliferative marker Ki 67 was 80%, the number of NHL lesions 1 (1- 8), diameter 28 × 30 × 29 (11 × 16 × 20 to 85 × 76 × 65) mm. The fundamental finding in brain lymphoma MRI imaging was lesion with predominantly homogenous contrast enhancement, diffusion restriction and collateral edema. Thirteen out of 27 (48%) patients underwent lumbar puncture, and lymphoma presence in fluid was detected in only two of them. The most frequent symptoms were limb paresis or hemiparesis (55%), bradypsichysm (22%), expressive aphasia (22%), cephalea (18%). Corticosteroid therapy, as a primary treatment option, was indicated in 15% of patients with a median overall survival of one month, CNS radiotherapy in 37% with a median survival of three months, and chemotherapy in 48% patients with a median overall survival 10 (2- 45) months. The brain lymphomas are rare and prognostically very unfavorable affection. When specifying brain focal lesions on MRI, it is necessary to consider this etiology and to elect imaging protocols with contrast agents and diffusion weighted sequence. Biopsy should be performed prior to start of corticosteroid therapy. Intensive chemotherapy or radiotherapy indication must be individually considered, and proposed treatment should be initiated immediately with a potential for somewhat prolonged survival.

Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid under naturalistic conditions

Introduction: To investigate whether drug concentrations in plasma can be considered as a valid surrogate marker of concentrations in brain/cerebrospinal fluid, the concentrations of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) in plasma and cerebrospinal fluid (CSF) were measured in 18 patients diagnosed with a depressive Episode in stable maintenance therapy. Method: The present study is a naturalistic prospective investigation of 18 depressive patients treated daily doses of venlafaxine extended release in a dose range between 75 and 300 mg. Patients underwent lumbar puncture (LP) for medical reasons and not for the purpose of this study. Blood was collected in at the same time as lumbar puncture was done. LP was done as part of the clinical routine without placing a special emphasis on trough levels of the ingested drug. Results: Plasma-levels of VEN were in a range between 10 and 1,269 ng/mL, ODV was in a range between 1 and 456 ng/mL. VEN + ODV (active moiety) correlated significantly with the oral venlafaxine dose (plasma: r =+0.810, p < 0.01; Pearson's correlation). CSF-levels were between 0 and 945 ng/mL for VEN, and 0 and 380 ng/mL for ODV. The correlation between plasma levels of VEN + ODV (active moiety) and the daily oral venlafaxine dose was highly significant and the correlation between the active moiety in plasma and CSF as well. Conclusion: The preliminary data of this ongoing study highlight the penetration of VEN and its active metabolite ODV into the CSF. In recent times, only few studies have addressed the question as to which extent plasma concentrations of psychotropic drugs correlate with CSF levels and knowledge is lacking concerning the impact of different drug levels in CSF on clinical outcome or on (cellular) homaeostasis within the CSF. The presented data show that in case of VEN and ODV, plasma concentrations can be considered as a valid surrogate marker of concentrations in CSF and possibly at its target structures inside the brain

A New Decision Tree Combining Abeta 1-42 and p-Tau Levels in Alzheimer&amp;apos;s Diagnosis

The objective of this work was to improve the clinical diagnosis of Alzheimer's disease (AD) by proposing a simple decision tree based on three major biomarkers of AD found in the cerebrospinal fluid (CSF): amyloid peptide Aβ1- 42, total Tau (t-Tau) and Tau phosphorylated at Thr181 (p-Tau). Two consecutive cohorts comprising 548 patients in total were recruited by the Memory and Neurology Clinics at Lille University Hospital (France). These included 293 patients with AD, 171 patients with other dementias and 84 healthy controls. All patients underwent lumbar puncture for the assessment of CSF concentrations of Aβ1-42, t-Tau and p-Tau. International criteria for dementias were used for diagnosis by investigators blind to CSF test results. To identify the combination of biomarkers that best predicted the 3 diagnoses, we used the CHAID decision tree method with the first cohort. Our analysis yielded a two-step decision tree, with a first stratification step based on the Aβ1-42/p-Tau ratio of the CSF, and a second step based on CSF p-Tau concentrations. The second cohort was then used to determine the power (0.618), sensitivity (82%) and specificity (81%) of this tree in AD diagnosis. These were found to be at least as high as those of other known algorithms based on the three CSF biomarkers, Aβ1-42, t-Tau and p-Tau.For the first time, diagnostic rules for AD based on CSF variables were compared in a single study. Our findings indicate that the measurement of Aβ1-42 and p-Tau levels in the CSF is sufficient to diagnose AD.

The Clinical Validity of the Spontaneous Retinal Venous Pulsation

The validity of the clinical dictum "the presence of spontaneous retinal venous pulsation (SVP) excludes raised intracranial pressure" has not been previously tested. We set out to determine the specificity and positive predictive value (PPV) of the presence of SVP to indicate normal intracranial pressure (ICP) in a routine clinical setting. We prospectively recruited patients undergoing lumbar puncture (LP), and 2 clinicians were blinded to the indications for LP and cerebrospinal fluid opening pressure (OP). Interobserver reliability was assessed. There were 106 patients in our cohort with a median age of 44 years (range, 18-79 years) and median body mass index of 27.5 kg/m (range, 18-48 kg/m). SVP was present in 94 of 106 patients (88.7%). Thirteen of 106 (12.3%) patients had high OP (≥30 cmH2O), and SVP was present in 11 of 13 patients (86%) with high OP. The sensitivity (95% confidence interval) of the presence of SVP to exclude raised ICP was 0.89 (0.88-0.92), specificity of 0.15 (0.05-0.37), PPV of 0.88 (0.87-0.9), and negative predictive value of 0.17 (0.05-0.4). Interobserver agreement was moderate for SVP (kappa = 0.42). Although the sensitivity and PPV of the presence of SVP to exclude raised ICP is high, it is not absolute. SVP can be seen in some patients with high ICP. Relying on the presence of SVP to exclude raised ICP may give a false sense of reassurance.

Poor correlation between intracranial pressure and intraocular pressure by hand-held tonometry

PurposeThe aim of this study is to provide data on the controversial issue of whether handheld measurements of intraocular pressure (IOP) are capable of accurately predicting elevated intracranial pressure (ICP) in patients undergoing lumbar puncture (LP).MethodsAll patients over the age of 18 years who underwent an LP in the emergency or neurological departments at the Tel Aviv Medical Center for any reason between October 2007 and July 2010 were eligible to participate in this prospective observational pilot study. IOP was measured with the Tono-Pen XL while patients were in the supine position before undergoing LP. ICP was measured in the lateral recumbent position. ICP and bilateral IOP were measured, and the mean and maximum values of IOP were calculated. The association between ICP and each one of the four IOP measures was evaluated by the Pearson correlation coefficient.ResultsTwenty-four patients (mean age 37.8 ± 15.8 years, ten males and 14 females) were enrolled. The reasons for their requiring an LP were headache (19/24 patients), evaluation for hemiparesis (2/24), cognitive deterioration (1/24), and seizures (2/24). Nine had elevated mean opening pressure (>20 cm H2O), six had an elevated mean IOP (>20 mmHg), and four of these six also had an elevated opening pressure. There was no significant correlation between the ICP measurements and any of the IOP measurements.ConclusionHandheld ocular tonometry has poor sensitivity and specificity for the prediction of increased ICP and is not an effective tool for screening for ICP in the ED or in the neurology department.