Identifying idiopathic intracranial hypertension in a hospital-based chronic headache population: Utility of magnetic resonance imaging, magnetic resonance venography and trans-orbital sonography.

BACKGROUND: One of the most underestimated types of chronic headaches is headaches as a result of cerebro-spinal fluid dysregulation disorders. Idiopathic intracranial hypertension (IIH) presents with headache and visual symptoms and usually is associated with papilledema. We identified patients with IIH in a chronic headache population presenting to a hospital-based headache clinic, and studied its associations with clinical, sonographic and magnetic resonance imaging (MRI) findings. METHODS: Of 168 patients, 141 chronic headache patients were identified and completed the study procedures (semi-structured medical interview, fundus examination, MRI brain with magnetic resonance venography (MRV) and trans-orbital sonography (TOS)). Patients with abnormal findings underwent lumbar puncture for opening pressure. RESULTS: The prevalence of IIH was 27%. IIH patients were of higher age, had gnawing/throbbing headache in the vertex in most cases, and had higher body mass index. Fundus examination had a sensitivity of 79% and a specificity of 98% for the detection of IIH cases. Approximately 23% of IIH patients had no papilledema. The most sensitive MR sign was found to be transverse sinus stenosis. TOS showed optic nerve sheath dilation in 35.7% of IIH without papilledema cases. CONCLUSIONS: The prevalence of IIH is high in the chronic headache population and should be suspected in the headache clinic setting, particularly because there is significant overlap with migraine symptomatology. MRI/MR venography and TOS can be useful adjunct tests to identify IIH patients.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

AIM OF THE STUDY: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. CLINICAL RATIONALE FOR STUDY: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. MATERIAL AND METHODS: 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF ß-amyloid 1-40 (Aß1-40), ß-amyloid 1-42 (Aß1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aß1-40/Aß1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. RESULTS: There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aß42/Aß40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). CONCLUSIONS: While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. CLINICAL IMPLICATIONS: These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.

Multiple neonicotinoids in children's cerebro-spinal fluid, plasma, and urine.

BACKGROUND: Neonicotinoids (NN) are selective neurotoxic pesticides that bind to insect but also mammal nicotinic acetycholine receptors (nAChRs). As the most widely used class of insecticides worldwide, they are ubiquitously found in the environment, wildlife, and foods, and thus of special concern for their impacts on the environment and human health. nAChRs are vital to proper brain organization during the prenatal period and play important roles in various motor, emotional, and cognitive functions. Little is known on children's contamination by NN. In a pilot study we tested the hypothesis that children's cerebro-spinal fluid (CSF) can be contaminated by NN. METHODS: NN were analysed in leftover CSF, blood, and urine samples from children treated for leukaemias and lymphomas and undergoing therapeutic lumbar punctions. We monitored all neonicotinoids approved on the global market and some of their most common metabolites by ultra-high performance liquid chromatography-tandem mass spectrometry. RESULTS: From August to December 2020, 14 children were consecutively included in the study. Median age was 8 years (range 3-18). All CSF and plasma samples were positive for at least one NN. Nine (64%) CSF samples and 13 (93%) plasma samples contained more than one NN. Thirteen (93%) CSF samples had N-desmethyl-acetamiprid (median concentration 0.0123, range 0.0024-0.1068 ng/mL), the major metabolite of acetamiprid. All but one urine samples were positive for ≥ one NN. A statistically significant linear relationship was found between plasma/urine and CSF N-desmethyl-acetamiprid concentrations. CONCLUSIONS: We have developed a reliable analytical method that revealed multiple NN and/or their metabolites in children's CSF, plasma, and urine. Our data suggest that contamination by multiple NN is not only an environmental hazard for non-target insects such as bees but also potentially for children.

Biomarkers of Dementia with Lewy Bodies: Differential Diagnostic with Alzheimer's Disease.

Dementia with Lewy Bodies (DLB) is a common form of cognitive neurodegenerative disease. Only one third of patients are correctly diagnosed due to the clinical similarity mainly with Alzheimer's disease (AD). In this review, we evaluate the interest of different biomarkers: cerebrospinal fluid (CSF), brain MRI, FP-CIT SPECT, MIBG SPECT, PET by focusing more specifically on differential diagnosis between DLB and AD. FP-CIT SPECT is of high interest to discriminate DLB and AD, but not at the prodromal stage (i.e., MCI). MIBG SPECT with decreased cardiac sympathetic activity, perfusion SPECT with occipital hypoperfusion, FDG PET with occipital hypometabolism and cingulate island signs are of interest at the dementia stage but with a lower validity. Brain MRI has shown differences in group study with lower grey matter concentration of the Insula in prodromal DLB, but its interest in clinical routines is not demonstrated. Concerning CSF biomarkers, many studies have already examined the relevance of AD biomarkers but also alpha-synuclein assays in DLB, so we will focus as comprehensively as possible on other biomarkers (especially those that do not appear to be directly related to synucleinopathy) that may be of interest in the differential diagnosis between AD and DLB. Furthermore, we would like to highlight the growing interest in CSF synuclein RT-QuIC, which seems to be an excellent discrimination tool but its application in clinical routine remains to be demonstrated, given the non-automation of the process.

No benefit of early versus late ambulation after incidental durotomy in lumbar spine surgery: a randomized controlled trial.

PURPOSE: Incidental durotomy (ID) is a complication occurring in 4-17% of decompressive spinal surgeries. Persisting CSF leakage can occur even after ID repair and requires revision surgery. Prolonged flat bed rest (BR) to reduce the incidence of persisting CSF leakage is frequently applied but highly debated. A randomized controlled trial comparing prolonged BR versus early ambulation after ID repair is lacking. The aim of this study was to investigate the incidence of revision surgery as a result of persistent cerebro-spinal fluid (CSF) leakage and medical complications after immediate or late post-operative ambulation following ID during decompressive spinal surgery. METHODS: Ninety-four of 1429 consecutive cases undergoing lumbar spine surgery (6.58%) were complicated by an ID. Sixty patients (mean age of 64 ± 13.28 years) were randomized to either early post-operative ambulation (EA, n = 30) or flat BR for 48 h (BR, n = 30). The incidence of CSF leakage resulting in revision surgery, medical complications and duration of hospitalization were compared between groups. RESULTS: Two patients in the BR group and two patients in the EA group underwent revision surgery as a result of persisting CSF leakage. Four patients in the BR group experienced medical complications associated with prolonged immobilization. The duration of hospitalization was 7.25 ± 3.0 days in the BR group versus 6.56 ± 2.64 days in the EA group, p = 0.413. CONCLUSION: The results of this study indicate no benefit of prolonged BR after an adequately repaired ID in lumbar spine surgery. LEVEL OF EVIDENCE: Level 1b (individual randomized controlled trial). These slides can be retrieved under Electronic Supplementary Material.

Alectinib's activity against CNS metastases from ALK-positive non-small cell lung cancer: a single institution case series.

In the present study we assessed the activity of the next-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) alectinib, in patients with ALK-postive, advanced non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases. NSCLCs with ALK-positive disease, as assessed by fluorescence in situ hybridization, and CNS metastases were treated with alectinib 600 mg BID. Included patients were followed prospectively in order to evaluate the efficacy of the drug, with particular emphasis on activity in the CNS. Eleven consecutive patients were enrolled. The majority of them were pretreated with crizotinib (n = 10, 90.9 %), and cranial radiotherapy (n = 8, 72.7 %). Six of the seven patients with measurable CNS disease experienced a CNS response, including three patients who were naïve for cranial radiation. Median duration of response was 8 months. For the whole population, median CNS-progression-free survival (-PFS), systemic-PFS, overall-PFS, overall survival, and 1-year survival were 8, 11, 8, 13 months, and 31.1 %, respectively. Two patients experiencing a CNS response were assessed for alectinib's concentrations in serum and cerebro-spinal fluid (CSF), and showed a CSF-to-serum ratio ranging from 0.001 to 0.003 ng/mL. Alectinib is highly active against CNS metastases from ALK-positive NSCLCs, irrespective of prior treatment(s) with ALK-TKI(s) and/or cranial radiotherapy. The low CSF-to-serum ratio of alectinib suggests that measuring the concentrations of the drug in the CSF may not be a reliable surrogate of its distribution into the CNS.

Ventriculo-peritoneal shunt independence following successful treatment of Gram negative (E. coli) ventriculitis: Case report and review of the literature.

We report a case of tumour-related hydrocephalus in a child treated with a ventriculo-peritoneal shunt which subsequently became infected with gram negative bacteria (Escherichia coli). After successful treatment of the infection the patient became shunt independent and has remained so for over 2 years. Gram negative ventriculitis is associated with diminished cerebro-spinal fluid production and we discuss the literature to date regarding this phenomenon.

Visualization of intra-thalamic nuclei with optimized white-matter-nulled MPRAGE at 7T.

Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classic Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders.

The hypervirulent Group B Streptococcus HvgA adhesin promotes central nervous system invasion through transcellular crossing of the choroid plexus.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of neonatal meningitis responsible for a substantial cause of death and disability worldwide. The vast majority of GBS neonatal meningitis cases are due to the CC17 hypervirulent clone. However, the cellular and molecular pathways involved in brain invasion by GBS CC17 isolates remain largely elusive. Here, we studied the specific interaction of the CC17 clone with the choroid plexus, the main component of the blood-cerebrospinal fluid (CSF) barrier. METHODS: The interaction of GBS CC17 or non-CC17 strains with choroid plexus cells was studied using an in vivo mouse model of meningitis and in vitro models of primary and transformed rodent choroid plexus epithelial cells (CPEC and Z310). In vivo interaction of GBS with the choroid plexus was assessed by microscopy. Bacterial invasion and cell barrier penetration were examined in vitro, as well as chemokines and cytokines in response to infection. RESULTS: GBS CC17 was found associated with the choroid plexus of the lateral, 3rd and 4th ventricles. Infection of choroid plexus epithelial cells revealed an efficient internalization of the bacteria into the cells with GBS CC17 displaying a greater ability to invade these cells than a non-CC17 strain. Internalization of the GBS CC17 strain involved the CC17-specific HvgA adhesin and occurred via a clathrin-dependent mechanism leading to transcellular transcytosis across the choroid plexus epithelial monolayer. CPEC infection resulted in the secretion of several chemokines, including CCL2, CCL3, CCL20, CX3CL1, and the matrix metalloproteinase MMP3, as well as immune cell infiltration. CONCLUSION: Our findings reveal a GBS strain-specific ability to infect the blood-CSF barrier, which appears to be an important site of bacterial entry and an active site of immune cell trafficking in response to infection.

Bulletproof Temporal Bone: A Case of Self-Inflicted Ballistic Injury.

Temporal bone injuries due to gunshot wounds are uncommon but devastating, with a high risk of damage to critical neurovascular structures. The high resistance of the temporal bone, the densest bone in the human body, can sometimes avoid a fatal outcome. However, the complications are in many cases devastating and include hearing loss, facial paralysis, cerebrospinal fluid leakage, intracranial damage, and vascular injuries. Our goal was to report a case of ballistic injury to the temporal bone and describe the surgical approach taken for treatment. A 74-year-old man was transferred to the emergency room of our tertiary hospital, intubated and sedated, after an attempted suicide with a firearm. The CT scan showed the metal projectile lodged within the temporal bone on the right side, with the destruction of the ossicular chain and bony labyrinth. After stabilization, sedation was reversed, and the otolaryngology team was called. On examination, the entry wound was located in the cavum concha, with no active bleeding but presenting active otorrhea of cerebrospinal fluid. The patient had complete peripheral facial paralysis on the right side and spontaneous horizontal nystagmus toward the left side. Empirical antibiotic therapy was initiated. A subtotal petrosectomy was performed, with the removal of the foreign body, repair of the cerebrospinal fluid fistula, obliteration of the cavity with abdominal fat, and closure of the external auditory canal. He was discharged on the 11th-day post-surgery, maintaining complete facial paralysis and right-side anacusis, but was able to walk with assistance. In conclusion, penetrating trauma of the temporal bone is a potentially life-threatening situation, and patients that survive have a guarded prognosis, as it often leads to permanent sequelae even when managed promptly.

Impact of early external ventricular drainage on functional outcome after traumatic brain injury: a bicentric retrospective cohort analysis.

PURPOSE: Several studies have confirmed that external ventricular drain decreases intracranial pressure (ICP) after traumatic brain injury (TBI). Considering its impact on ICP control and cerebral waste metabolites clearance, timing of external ventricular drain (EVD) insertion could improve CSF drainage efficiency. The aim of the study was to evaluate the impact of early EVD versus a later one on the 3-month outcome. METHODS: For this retrospective cohort study conducted in two regional trauma-center (Caen CHU Côte de Nacre and Beaujon Hospital) between May 2011 and March 2019, all patients with intracranial hypertension following TBI and treated with EVD were included. We defined the early EVD by drainage within the 24 h of the hospital admission and the late EVD insertion by drainage beyond 24 h. A poor outcome was defined as a Glasgow Outcome Scale of one or two at 3 months. RESULTS: Among the cohort of 671 patients, we analyzed 127 patients. Sixty-one (48.0%) patients had an early insertion of EVD. In the early EVD group, the mean time to insertion was 10 h versus 55 h in the late EVD group. Among the analyzed patients, 69 (54.3%) had a poor outcome including 39 (63.9%) in the early group and 30 (45.5%) in the later one. After adjustment on prognostic factors, early EVD insertion was not associated with a decrease in a poor outcome at 3-months (OR = 1.80 [0.73-4.53]). CONCLUSION: Early insertion of EVD (<24 h) for intracranial hypertension after TBI was not associated with improved outcome at 3 months.

Relation between Guillain-Barré syndrome and Covid-19: Case-Series.

Approximately two-thirds of the Guillain-Barré syndrome (GBS) cases are preceded by upper respiratory tract infection or enteritis. There has been previous documentation of a clear association between Covid-19 and GBS. Covid-19 can affect the nervous tissue either through direct damage or through triggering a host immune response with subsequent development of autoimmune diseases such as GBS. Covid-19 can affect the host`s immune system through the activation and interaction of the T-and B-lymphocytes with subsequent production of antibodies that cross-react with the gangliosides. Depending on the nature of the neuronal autoimmune destruction, the affected individual may have either a demyelinating or axonal subtype of GBS. These subtypes differ not only in symptoms but also in the likelihood of recovery. This report presents two cases of GBS that developed after the respiratory symptoms of Covid-19. Their neurological features indicated demyelination, axonal damage, irritation of spinal nerve roots, and impaired sensory and motor transmission with additional facial nerve palsy in the second-studied case. This case report highlights the relationship between GBS and Covid-19 infection.

Seizure and neuropsychiatric compromise as onset of SARS-CoV-2 associated encephalitis.

Infectious SARS-CoV-2 meningitis is rare, especially as the first manifestation of a SARS-CoV-2 infection. Infectious SARS-CoV-2 meningitis can initially manifest with seizures and neuropsychiatric abnormalities, worsen to the point of coma, and occasionally lead to death. Patients with infectious SARS-CoV-2 meningitis require comprehensive evaluation and forced treatment in order to improve the often poor outcome.

Type, management, and associated factors of failed spinal anesthesia in cesarean section. Prospective cohort study.

Background: Spinal anesthesia is an anesthesia technique suitable for cesarean section to avoid respiratory complications. However, the management of spinal anesthesia is very important because spinal anesthesia may fail and the patient may be exposed to pain and discomfort. Objective: To assess the type, management, and related factors of failure of spinal anesthesia at cesarean section. Methods: Multicenter prospective cohort study was conducted at a public hospital in Addis Ababa on 794 mothers who met the criteria for cesarean section under spinal anesthesia. Data collection methods were adopted, including chart reviews and observations of spinal anesthesia procedures. The data collected was entered in Epi info version 7 and analyzed in SPSS version 20. Independent variables with dependent variables were analyzed using logistic regression. A p-value of 0.05 for & it; was considered a statistically significant test cutoff. Result: Of 121 failed spinal anesthesia 35 were complete and 86 were partial failed spinal anesthesia from those complete failed spinal anesthesia were managed by repeating spinal and converting to general anesthesia and partial failed spinal anesthesia were managed by the supplementary drug. Experience of the anesthetist <1 (AOR = 4.12, 95% CI, 2.47-6.90), patient position (AOR = 14.43,95%CL, 2.65-78.61), number of attempts>1 (AOR = 9.26, 95% CI, 5.69-15.01), bloody CSF (AOR = 6.37, 95%CI, 2.90-13.96), BMI ≥30kgm2 (AOR = 2.03, 95%CI, 1.12-3.68) and dose of bupivacaine <10 mg (AOR = 2.72, 95% CI, 1.33-5.53) were found to be statistically significant associated with failed spinal anesthesia. Conclusion and recommendation: Experience of anesthetists (<1 year), obesity, bupivacaine dose <10 mg, bloody appearance of CSF, number of attempts> 1 were associated factors for failed spinal anesthesia in cesarean section. Our failed spinal management is not the same among hospitals and does not follow recommended failed spinal management. Up-skilling of anesthesia professionals should be considered on identified associated factors of failed spinal anesthesia and management of failed spinal anesthesia should be based on the recommended guidelines.

Diagnosis and treatment of noncommunicating extradural spinal thoracolumbar arachnoid cyst.

BACKGROUND: Noncommunicating extradural spinal arachnoid cysts are extremely rare. They are believed to arise from congenital defects in the dura mater and become enlarged as a consequence of increased cerebro-spinal fluid (CSF) pressure within the subarachnoid space. Most retain a communicating pedicle through which the extradural cyst maintains connection with the subarachnoid space, and only rarely does this communication become sealed. The optimal treatment consists of complete surgical removal of the cyst with ligation of the communicating pedicle. CASE DESCRIPTION: A 29-year-old male presented with a progressive spastic paraparesis of 6 months' duration. The MRI showed a circumscribed intradural extramedullary cystic lesion located from D11-L2. Notably, peroperatively, the cyst appeared to be entirely extradural, without a communicating intradural pedicle. Further, no CSF leak was observed even after Valsalva maneuvers. Following surgical extirpation of the cyst, the patient sustained an uneventful recovery within 1 postoperative month. CONCLUSION: Noncommunicating extradural arachnoid cysts are extremely rare causes of spinal cord compression and should be fully excised.

Diagnostic value of cerebro-spinal fluid biomarkers in dementia with lewy bodies.

Dementia with Lewy Bodies (DLB) is the second most common form of dementia after Alzheimer's disease (AD), accounting for 15% to 20% of neuropathologically defined cases. Two-thirds of the patients affected are not or misdiagnosed because of the clinical similarity of these two pathologies. In this review, we evaluate the discriminatory power of cerebrospinal fluid (CSF) biomarkers by focusing more specifically on differential diagnosis between DLB and AD. We focus on the AD biological biomarkers used in clinical routine as well as the biomarkers under study and more particularly the alpha-synuclein assay. Thus, among the AD biomarkers (t-Tau, phospho-Tau181, Aß42 and Aß40) used routinely, t-Tau and phospho-Tau181 have shown excellent discrimination whatever the clinical stages severity. Aß42 level is pathological in DLB patients at the demented stage, but is almost not impacted at the prodromal stage. Alpha-synuclein assay in the CSF has also an interest in the discrimination between DLB and AD but not in segregation between DLB and healthy elderly subjects. Thus, globally the biological diagnosis on CSF basis makes it possible, to separate the DLBs from the ADs. In addition, the development of biomarkers such as phospho-alpha-synuclein and oligomeric alpha-synuclein should help to reinforce this discrimination power.

Previously Diagnosed Leber's Hereditary Optic Neuropathy with Clinical Signs of Idiopathic Intracranial Hypertension Responsive to Acetazolamide Therapy.

PURPOSE: To present a case of suspected Leber's hereditary optic neuropathy (LHON) with MRI and OCT findings compatible with pseudotumor cerebri responsive to acetazolamide therapy. CASE REPORT: A five-year-old boy referred to our clinic with optic atrophy and low vision was originally diagnosed with LHON. Laboratory tests were negative for LHON, while OCT and MRI were consistent with pseudotumor cerebri. Acetazolamide therapy resulted in dramatic improvement of visual acuity. CONCLUSION: Some cases of previously labeled hereditary optic neuropathies with clinical signs of idiopathic intracranial hypertension could respond to intracranial pressure lowering treatment.

The common cavity vs incomplete partition type I conundrum: Decision making and management with the cochlear implant form electrode.

It has been seen that 20% of children with deafness have inner ear malformations. Studies demonstrate that Cerebrospinal Fluid (CSF) leakage occurs in 40-50% of patients with inner ear malformations. Differentiating between the various malformations pre-operatively allows the cochlear implant surgeon to plan and prepare for various difficulties associated with the management of such cases. In case of a CSF gusher, a choice of an electrode with a stopper helps in effectively closing off the cochleostomy, thus reducing the chances of post-operative infections. Case description: SM, a 10-year-old girl with the diagnosis of bilateral progressive profound hearing loss showed cochlear malformations on high resolution computed tomography (HRCT) scans of the temporal bones. A detailed study and discussion with the neuro-radiologist helped in identifying the cochleo-vestibular malformations (CVM) on both sides, thus making the choice of the better ear for electrode insertion and the type of electrode. She was subjected to left ear cochlear implantation using a lateral canal labyrinthotomy approach and a Form electrode (Med El®) with a special conical stopper was used to effectively seal the labyrinthostomy. Conclusion: Common cavity (CC) and Incomplete Partition (IP) Type I present as diagnostic challenges. Getting to the right diagnosis is of paramount importance as it helps in deciding the correct ear, choosing the correct electrode, and preparing for the surgical situations the surgeon might encounter. The Form electrode shows promise due to its unique conical seal which helps in preventing CSF leakage, thus reducing the chances of post-operative infections in cases of deformed cochlea.

LC-MS application for therapeutic drug monitoring in alternative matrices.

Nowadays the practice of therapeutic drug monitoring, consisting in the measurement of drugs concentrations in biological matrices in order to guide possible posological adjustments, is becoming more and more important for the management and optimization of several treatments, especially when drugs with narrow therapeutic indexes are administered. Although TDM on plasma samples is currently considered the gold standard, this practice shows some limitations: it requires venous blood sampling, centrifugation and, if necessary, shipment with refrigeration; moreover, drug concentrations in plasma or blood do not necessarily reflect the ones in the target tissues or cells. Therefore, in the recent years great attention has been given to alternative matrices for TDM purpose, in order to reduce invasiveness, costs or to obtain better information about drug concentrations at the active sites. This evolution is strongly sustained by the spreading use of liquid chromatography coupled with mass spectrometry (LC-MS) techniques for the analysis of small molecules, which is constantly increasing sensitivity and specificity of TDM assays. In this review, we present and summarize recently published LC-MS applications providing alternatives to plasma testing, in order to avoid blood withdrawal, plasma separation, refrigerated shipment or, if possible, to obtain better information about drug exposure in target cells. By analyzing the last 5 years of literature, reported in PubMed website, LC-MS/MS applications have been reported, with particular focus on the ones with higher probability to enter in the near future in clinical practice. Microsampling strategies and alternative biological matrices, from urine to tissue samples, have been included.

Disease activity in progressive multiple sclerosis can be effectively reduced by cladribine.

BACKGROUND: Evidence suggests people with non-relapsing deteriorating ("progressive") multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices. METHODS: We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment. RESULTS: Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS. CONCLUSIONS: pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS.