Treatment of metastatic cutaneous squamous cell carcinoma in a solid organ transplant recipient with programmed death-1 checkpoint inhibitor therapy.

Limited data exist on the use of immune checkpoint inhibitors (ICI) for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTR). We report a case of a SOTR who developed metastatic disease following multiple surgeries, three cycles of adjuvant radiotherapy, and minimization of immunosuppression. He was subsequently treated with pembrolizumab and achieved a complete response. However, the patient developed ICI-induced allograft rejection requiring therapy discontinuation. The allograft was salvaged following IVIg and steroids. The patient developed recurrent disease which failed rechallenge with pembrolizumab but achieved a partial response following cemiplimab administration. This case illustrates the potential to treat metastatic CSCC in a SOTR with anti-programmed death-1 therapy and preserve graft function despite allograft rejection.

Clinical anxiety promotes excessive response inhibition.

BACKGROUND: Laboratory tasks to delineate anxiety disorder features are used to refine classification and inform our understanding of etiological mechanisms. The present study examines laboratory measures of response inhibition, specifically the inhibition of a pre-potent motor response, in clinical anxiety. Data on associations between anxiety and response inhibition remain inconsistent, perhaps because of dissociable effects of clinical anxiety and experimentally manipulated state anxiety. Few studies directly assess the independent and interacting effects of these two anxiety types (state v. disorder) on response inhibition. The current study accomplished this goal, by manipulating state anxiety in healthy and clinically anxious individuals while they complete a response inhibition task. METHOD: The study employs the threat-of-shock paradigm, one of the best-established manipulations for robustly increasing state anxiety. Participants included 82 adults (41 healthy; 41 patients with an anxiety disorder). A go/nogo task with highly frequent go trials was administered during alternating periods of safety and shock threat. Signal detection theory was used to quantify response bias and signal-detection sensitivity. RESULTS: There were independent effects of anxiety and clinical anxiety on response inhibition. In both groups, heightened anxiety facilitated response inhibition, leading to reduced nogo commission errors. Compared with the healthy group, clinical anxiety was associated with excessive response inhibition and increased go omission errors in both the safe and threat conditions. CONCLUSIONS: Response inhibition and its impact on go omission errors appear to be a promising behavioral marker of clinical anxiety. These results have implications for a dimensional view of clinical anxiety.

A decade of Clostridioides difficile infection: a constant challenge to maintain the status quo.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea. We retrospectively investigated data from a comprehensive, multidisciplinary C. difficile surveillance programme focusing on hospitalized patients in a tertiary Irish hospital over 10 years. METHODS: Data from 2012 to 2021 were extracted from a centralized database, including patient demographics, admission, case and outbreak details, ribotypes (RTs), and (since 2016) antimicrobial exposures and CDI treatments. Counts of CDI by origin of infection were explored using ꭓ2 analyses, Poisson regression was used to investigate trends in rates of CDI and possible risk factors. Time to recurrent CDI was examined by a Cox proportional hazards regression. RESULTS: Over 10 years, 954 CDI patients had a 9% recurrent CDI rate. CDI testing requests occurred in only 22% of patients. Most CDIs were HA (82.2%) and affected females (odds ratio: 2.3, P<0.01). Fidaxomicin significantly reduced the hazard ratio of time to recurrent CDI. No trends in HA-CDI incidence were observed despite key time-point events and increasing hospital activity. In 2021, community-associated (CA)-CDI increased. RTs did not differ for HA versus CA for the most common RTs (014, 078, 005 and 015). Average length-of-stay differed significantly between HA (67.1 days) and CA (14.6 days) CDI. CONCLUSION: HA-CDI rates remained unchanged despite key events and increased hospital activity, whereas by 2021, CA-CDI was at its highest in a decade. The convergence of CA and HA RTs, and the proportion of CA-CDI, question the relevance of current case definitions when increasingly patients receive hospital care without an overnight hospital stay.

Multidisciplinary neurosurgical rounds incorporating antimicrobial stewardship. Are they of benefit?

Background: In an era of increasing antimicrobial resistance, appropriate antimicrobials are essential to optimise patient outcomes. In 2017, antimicrobial use prevalence (AMU) on the two neurosurgical wards in our tertiary teaching hospital varied from 23% on ward A to 33% on ward B with 67% and 100% 'appropriate' prescriptions, respectively. In July 2018, a weekly antimicrobial stewardship multidisciplinary round led by a senior neurosurgery registrar commenced, attended by the antimicrobial stewardship team (AST). Research question: This report evaluates whether a multi-disciplinary approach on neurosurgical prescribing was beneficial, specifically in reducing AMU. Materials and methods: The following data was collected on AST rounds for 30 weeks in total from August 2018 to July 2019: number of patients on antimicrobials, appropriateness and stewardship actions. A questionnaire was distributed to neurosurgical doctors on two occasions to canvass opinions and attitudes on antimicrobial prescribing. Results: 1716 prescriptions were reviewed (mean 57.2 per week). Of these 321 (18.7%) included antimicrobial prescriptions; 200 on ward A (19.8%), and 121 on ward B (17%), representing a decrease in AMU from 2017. The majority of antimicrobial prescriptions, 271 (84.4%) were deemed appropriate. Stewardship actions were taken in 215 (67%) prescriptions.Fifteen questionnaires were completed by neurosurgical doctors. The majority, 87%, stated the AST round was helpful overall. 93% indicated that informal training on the AST round was a source of education in antibiotic prescribing. Discussion and conclusion: The weekly AST round provided a timely opportunity for multidisciplinary discussion, implementation of antimicrobial stewardship actions and opportunistic antimicrobial stewardship education.

COL6A1 gene and Ironman triathlon performance.

Mutations in the type VI collagen gene ( COL6A1) cause myopathy and muscle weakness. In addition, COL6A1 knockout mice were shown to have impaired running performance and reduced muscle strength. The COL6A1 rs35796750 polymorphism (IVS32-29 T/C) has been associated with complex phenotypes. The aim of this study was therefore to determine if this polymorphism is associated with performance during the 226 km Ironman triathlon. Participants (n=661) were recruited during 4 South African Ironman triathlons. Finishing times for the 3.8 km swim, 180 km bike, 42.2 km run, and overall race were provided by the race organisers. All participants were genotyped for the COL6A1 rs35796750 polymorphism. Participants with the COL6A1 TT genotype were significantly faster during the bike (p=0.014) and overall race (p=0.030). When participants were grouped into fast, middle and slow bike finishing time tertiles, there was a significant linear trend for the TT genotype (Fast: TT=35.7%; Middle: TT=29.0%; Slow: TT=23.8%; p=0.008). No significant genotype frequency differences were observed for the swim or run of the triathlon. In conclusion, the COL6A1 gene is therefore a potential marker for endurance cycling performance. These effects may be mediated through changes to the composition of type VI collagen containing tissues, such as muscle and tendon.

Antifungal susceptibility testing and candidaemia at a tertiary referral hospital.

Candidaemia is associated with a high mortality. We have reviewed cases of candidaemia over a 2-year period at a tertiary referral hospital in association with the introduction of routine antifungal susceptibility testing. The aim of the study was two fold; firstly to establish the typical profile of a patient who might experience a Candida bloodstream infection and secondly, to evaluate methods of antifungal susceptibility testing. In 2008-2009, 31 patients with candidaemia were retrospectively identified using the Laboratory Information Systems (Apex). Clinical data were obtained by chart review. Antifungal susceptibility testing to fluconazole and voriconazole was carried out on 20 of the clinical isolates using three different methods. These isolates were also sent to the mycology reference laboratory at Bristol and results were compared. The male-to-female ratio was 2.1:1 with an age range from 6 weeks to 89 years. Candida albicans was the predominant species (n= 17). Patients were predominantly general surgical (39%), oncology (16%) and urology (13%). Identified risk factors included treatment with broad-spectrum antimicrobial agents (89%), central venous catheters (CVCs) (89%), and surgery during the current admission (54%). The crude mortality rate (death prior to discharge) was 42%. Only 1 of the 20 isolates tested, a Candida glabrata, tested resistant to fluconazole. Of 3 antifungal susceptibility test systems evaluated (VITEK 2, TREK Sensititre YeastOne and CLSI disk diffusion); the VITEK 2 system was considered most appropriate for routine use in our laboratory. Retrospective review of therapy identified 7 patients treated with echinocandins in whom susceptibility testing indicated that fluconazole could have been used with significant reduction in cost of therapy.

Evolving epidemiology of carbapenemase-producing Enterobacterales: one hospital's infection prevention and control response over nine years.

BACKGROUND: Preventing carbapenemase-producing Enterobacterales (CPE) transmission is a significant challenge for hospital infection prevention and control teams (IPCTs). Control measures include screening at-risk patients, contact tracing, and the isolation of carriers with contact precautions. AIM: The evolution of infection prevention and control measures was assessed in a tertiary acute care hospital with predominately multi-bedded patient accommodation, from 2011 to 2019 as cases of CPE increased. The implications for, and the response and actions of, the IPCT were also reviewed. METHODS: CPE data collected prospectively from our laboratory, IPCT, and outbreak meeting records were reviewed to assess how the IPCT adapted to the changing epidemiology, from sporadic cases, to outbreaks and to localized endemic CPE. FINDINGS: Of 178 cases, 152 (85%) were healthcare-associated and there was a marked increase in cases from 2017. The number of screening samples tested annually increased from 1190 in 2011 to 16,837 in 2019, and six outbreaks were documented, with larger outbreaks identified in later years. OXA-48 carbapenemase was detected in 88% of isolates and attendance at outbreak meetings alone accounted for 463.5 h of IPCT members, and related staff time. CONCLUSION: Despite considerable efforts and time invested by the IPCT, the number of CPE cases is increasing year-on-year, with more outbreaks being reported in later years, albeit partly in response to increased screening requirements. Infrastructural deficits, the changing epidemiology of CPE, and national policy are major factors in the increasing number of cases.

Hepatitis B virus infection in children.

Recent increases in Hepatitis B virus (HBV) infection prompted us to characterize HBV-infected children in Ireland and to audit management, by reviewing prospectively gathered data. Of 46 children (29 [63%] male), median age at presentation was 8.1 years (range 0.6-17.6), monitoring duration was 22.5 months (range 1-101), 23/46 (50%) were European (including 9 [19.6%] Irish), 15 (32.6%) African and 9 (19.6%) Asian. Acquisition was vertical (25/46 [54.3%]), horizontal (5/46 [10.9%]), unknown (16/46 [34.8%]). HBV-DNA was >100,000,000 cpm in 20/32 (62.5%) with chronic infection. Hepatitis B e antigen (HBeAg) was detected in 32/44 (72.7%). We estimate that universal neonatal vaccination (UNV-HBV) could have prevented 22% of cases, and could limit further horizontal HBV spread. This supports the recent introduction of UNV-HBV.

Food for thought. Malnutrition risk associated with increased risk of healthcare-associated infection.

BACKGROUND: Infection and malnutrition are interconnected. UK and Irish guidelines recommend the Malnutrition Universal Screening Tool (MUST) for nutritional risk screening. Patients with a MUST score of ≥2 are considered at high risk of malnutrition and referral for nutritional assessment is recommended. AIM: To explore the association between healthcare-associated infection (HCAI) and the MUST score categories of patients. METHODS: This was a cross-sectional study in May 2017 on ten representative wards in our institution. Patient demographics, MUST score, presence of medical devices, HCAI and antimicrobial use were collected. FINDINGS: Of 240 patients, the HCAI prevalence was 10.4% (N = 25) and 26% (N = 63) were at high risk of malnutrition (MUST score ≥2). Patients with HCAI were more likely to have had surgery (odds ratio (OR): 5.5; confidence interval (CI): 2.1-14.3; P < 0.001), a central vascular catheter (OR: 10.0; CI: 3.6-27.2; P < 0.001), or a urinary catheter in situ (OR: 7.5; CI: 2.8-20.0; P < 0.001), and to have a high risk of malnutrition (OR: 4.3; CI: 1.7-11.2; P < 0.001). A higher MUST score remained a significant predictor of a patient having HCAI on multivariate regression analysis (CI: 0.2-0.6; P < 0.001). CONCLUSION: Patients at risk of malnutrition when assessed with the MUST were more likely to have HCAI. However, prospective studies are required to investigate the temporal association between MUST and HCAI and which interventions best address malnutrition risk and HCAI reduction in different settings.

Characterisation of Yersinia pestis isolates from natural foci of plague in the Republic of Georgia, and their relationship to Y. pestis isolates from other countries.

Forty Yersinia pestis isolates from endemic foci of plague in the Republic of Georgia, and six Y. pestis isolates from neighbouring former Soviet Union countries, were analysed for their biochemical and phenotypic properties, and their genetic relatedness was compared with Y. pestis strains KIM and CO92 by pulsed-field gel electrophoresis (PFGE). In addition, 11 Y. pestis isolates from the USA, together with published nucleotide sequences from Y. pestis strains KIM, CO92 and 91001, were compared with the 46 isolates in the present collection using multilocus sequence typing (MLST), based on sequence data for the 16S rRNA, hsp60, glnA, gyrB, recA, manB, thrA and tmk loci. Four virulence gene loci (caf1, lcrV, psaA and pla) were also sequenced and analysed. Two sequence types (ST1 and ST2), which differed by a single nucleotide, were identified by MLST. With the exception of a single isolate (771G), all of the Georgian Y. pestis isolates belonged to ST2. PFGE also grouped the Georgian Y. pestis isolates separately from the non-Georgian isolates. Overall, PFGE discriminated the Y. pestis isolates more effectively than MLST. The sequences of three of the four virulence genes (lcrV, psaA and pla) were identical in all Georgian and non-Georgian isolates, but the caf1 locus was represented by two allele types, with caf1 NT1 being associated with the non-Georgian isolates and caf1 NT2 being associated with the Georgian isolates. These results suggest that Georgian Y. pestis isolates are of clonal origin.

Headaches in a rheumatology clinic: when one pain leads to another.

Chronic daily headaches (CDH) affect between 3 and 4% of the Western population and is one of the most common problems seen in the neurology clinic. It is often difficult to delineate where CDH began and medication overuse headache (MOH) supervenes. The current study analyses the development of MOH in people taking regular analgesia for reasons other than headache, namely patients attending rheumatology clinics. The aim of this study was to assess, for the first time in an Irish population of patients, whether CDH was more common in such patients as previously reported. We also wanted to see how often rheumatology patients were taking non-prescribed analgesics. The results show that, in a cohort of 114 rheumatology patients, 32% reported that they suffer from headaches regularly. Of these, 38% fulfilled criteria for CDH (or 12% of the whole cohort). Of the 14 patients with CDH, 11 also fulfilled the International Classification of Headache Disorders criteria for MOH. Seventy per cent of the patients fell under the category of medication overuse (>15 days a month for > 3 months) but only 9% fulfil criteria for MOH. Contrary to the previous work in this area, we found a very low (< 2 %) incidence of previous migraine in our patients with CDH. We conclude that headaches (both CDH and MOH) are common in this patient population. We suggest that here should be greater awareness amongst all doctors caring for these patients of the potential for creating a second chronic problem when using excessive analgesia to treat the first.

Canine T cell lymphoma treated with lomustine, vincristine, procarbazine, and prednisolone chemotherapy in 35 dogs.

Canine T cell lymphoma has previously been found to be a poor prognostic indicator compared with its B cell counterpart. The cyclophosphamide, doxorubicin, vincristine, and prednisolone protocol is widely accepted as a first line treatment for canine lymphoma. There have been several studies investigating alternative protocols for T cell lymphoma. This study investigated the use of a modified lomustine, vincristine, procarbazine and prednisolone protocol as a first line treatment in 35 dogs with T Cell lymphoma. Median progression free survival (PFS) time for all 35 dogs was 431 days with a 6-month, 1-year, 2-year, and 3-year PFS of 69%, 54%, 29%, and 12%. Median survival time (MST) was 507 days. Twenty-nine dogs attained a complete response and had a median PFS time of 509 days. Thirty dogs experienced adverse events during the protocol, with 73% of these being grade 1 or 2. This protocol has shown increased median PFS time and MST compared with previous studies and suggests its use as a first line chemotherapy protocol against canine T cell lymphoma.

Cognitive dysfunction in early multiple sclerosis: a review.

Cognitive impairment is a common and disabling feature of Multiple Sclerosis (MS), including early MS, and may even pre-date any physical symptoms. It contributes even more to withdrawal from work than physical disability. Here, we provide an overview of cognitive impairment in MS, particularly in early MS where it is most commonly under-reported and under-treated. We address the presenting features of CI, its impact on quality of life, and its validated assessments (in particular the use of Brief International Cognitive Assessment in MS for use in a clinical setting). We review the insights radiology has given us into the pathogenesis of cognitive impairment in MS, particularly in early CI and in cognitively preserved MS patients. We review current treatments for cognitive impairment, primarily cognitive rehabilitation. We address the evidence for its associated co-morbidities, which may exacerbate or trigger CI, and should therefore be addressed early in the disease course (smoking, alcohol, mood, fatigue and potential co-existing sleep disorders, exercise, and vitamin D). The article supports the importance for early recognition and management of cognitive impairment in MS, before it becomes an established and irreversible entity.

The potential contribution of 16S ribosomal RNA polymerase chain reaction to antimicrobial stewardship in culture-negative infection.

Empiric broad-spectrum antimicrobial therapy frequently results in culture-negative specimens making rationalization of therapy difficult. We retrospectively reviewed 16S rRNA polymerase chain reaction (PCR) results from 78 specimens in 60 patients. 16S rRNA was detected in 28 (47%) patients with de-escalation of therapy in five (21%). Microbial DNA was not detected in 32 (53%) patients with antimicrobials discontinued in two (8%). Neurosurgical patients had a higher proportion of positive results (53% vs 34%) and treatment rationalizations (17% vs 12%). In specific patient groups, 16s rRNA PCR is a useful antimicrobial stewardship tool for targeting antimicrobial therapy.

Role of the Saccharomyces cerevisiae general regulatory factor CP1 in methionine biosynthetic gene transcription.

Saccharomyces cerevisiae general regulatory factor CP1 (encoded by the gene CEP1) is required for optimal chromosome segregation and methionine prototrophy. MET16-CYC1-lacZ reporter constructs were used to show that MET16 5'-flanking DNA contains a CP1-dependent upstream activation sequence (UAS). Activity of the UAS required an intact CP1-binding site, and the effects of cis-acting mutations on CP1 binding and UAS activity correlated. In most respects, MET16-CYC1-lacZ reporter gene expression mirrored that of chromosomal MET16; however, the endogenous gene was found to be activated in response to amino acid starvation (general control). The latter mechanism was both GCN4 and CP1 dependent. MET25 was also found to be activated by GCN4, albeit weakly. More importantly, MET25 transcription was strongly CP1 dependent in gcn4 backgrounds. The modulation of MET gene expression by GCN4 can explain discrepancies in the literature regarding CP1 dependence of MET gene transcription. Lastly, micrococcal nuclease digestion and indirect end labeling were used to analyze the chromatin structure of the MET16 locus in wild-type and cep1 cells. The results indicated that CP1 plays no major role in configuring chromatin structure in this region, although localized CP1-specific differences in nuclease sensitivity were detected.

GCP5 and GCP6: two new members of the human gamma-tubulin complex.

The gamma-tubulin complex is a large multiprotein complex that is required for microtubule nucleation at the centrosome. Here we report the purification and characterization of the human gamma-tubulin complex and the identification of its subunits. The human gamma-tubulin complex is a ring of ~25 nm, has a subunit structure similar to that reported for gamma-tubulin complexes from other species, and is able to nucleate microtubule polymerization in vitro. Mass spectrometry analysis of the human gamma-tubulin complex components confirmed the presence of four previously identified components (gamma-tubulin and gamma-tubulin complex proteins [GCPs] 2, 3, and 4) and led to the identification of two new components, GCP5 and GCP6. Sequence analysis revealed that the GCPs share five regions of sequence similarity and define a novel protein superfamily that is conserved in metazoans. GCP5 and GCP6, like other components of the gamma-tubulin complex, localize to the centrosome and associate with microtubules, suggesting that the entire gamma-tubulin complex takes part in both of these interactions. Stoichiometry experiments revealed that there is a single copy of GCP5 and multiple copies of gamma-tubulin, GCP2, GCP3, and GCP4 within the gamma-tubulin complex. Thus, the gamma-tubulin complex is conserved in structure and function, suggesting that the mechanism of microtubule nucleation is conserved.

Incidence of multiple sclerosis in the Republic of Ireland: A prospective population-based study.

BACKGROUND: Multiple sclerosis (MS) incidence and prevalence is increasing worldwide, with a disproportionally higher rate in women. Recent studies have questioned the presence of a latitudinal gradient in Europe. Ireland is a high prevalence country for MS with a previously reported North-South gradient making it ideal to further explore this concept. OBJECTIVES: In this study we prospectively determined the incidence rate of newly diagnosed MS in Ireland over a 12-month period and demonstrated the presence of a North-South gradient. METHODS: A national prospective population-based observational study was performed to ascertain all new cases of MS diagnosed from 1st March 2014 - 28th February 2015 in the Ireland. Within the main study there was a smaller nested cohort study to explore clinical outcomes with a view to future prospective follow-up of this cohort. Sources of case ascertainment included neurologists, MS nurse specialists and MS support services. The Irish census 2011 was used to obtain population statistics and the incidence rate was age-standardized to a European Standardised Population (ESP 2011). The North-South gradient was assessed, by comparing incidence rates between northern and southern counties. RESULTS: 292 patients fulfilled the inclusion criteria equating to an age-standardised incidence rate (A-SIR) of 6/100,000 (95% CI: 5.3-6.6); for women the rate was 8.7/100,000 (95% CI: 7.7-9.6) and for men 3.3/100,000 (95% CI: 3.0-3.7). The female to male sex ratio was 2.7:1. Mean age at diagnosis amongst the RRMS group was 37 years (SD: 9.6) and 55 years (SD: 7.7) in the PPMS group; there were no gender differences associated with age of diagnosis. Onset was progressive in 10% of cases. A significant difference was seen in incidence rates between the northern region (A-SIR: 9.6×105, CI: 6.9-12.3) and the southern region (A-SIR: 5.1×105, CI: 3.8-6.3) (Z-score =3.34, p<0.05). Amongst the nested cohort (n=113) mean age at symptom onset in the RRMS group (n=106) was 34 years (SD: 8.7) and 50 years (SD: 11.8) in the PPMS group (n=7). The female to male sex ratio was 3.5:1. Eighty percent had started or were due to start disease modifying therapy at time of review and 77% were taking supplemental vitamin D. Using the hospital depression and anxiety scale (HADS) mild to severe depressive symptoms were reported in 34% with no prior history of depression. Seventy-five percent were in full or part-time employment with 8% not working due to disability arising from their MS. CONCLUSIONS: This is the first study to prospectively assess the incidence rate of MS in Ireland and shows that Ireland has a high incidence rate, comparable with the rest of the British Isles, with a persistent North-South gradient. The age of onset of relapsing remitting multiple sclerosis appears to be increasing over the last 20 years. It will be of interest to re-assess this population over time to see if increasing incidence rates, as well as improved survival, are driving the reported increases in MS prevalence.

Neurosarcoidosis: clinical presentations and changing treatment patterns in an Irish Caucasian population.

BACKGROUND: The clinical manifestations of neurosarcoidosis are highly variable and it should be considered as a potential differential diagnosis in any neurological presentation. AIM: This study was designed to describe the clinical, diagnostic, and treatment patterns and functional outcome in a Caucasian neurosarcoidosis population. DESIGN: A retrospective analysis was performed on prospectively recorded data in patients attending our neurology clinic between 2008 and 2014 with a diagnosis of definite or probable neurosarcoidosis according to Zajiek criteria. METHODS: Detailed clinical features, baseline demographic data, results of investigations, treatment type and duration, and clinical outcomes were collated. RESULTS: Eleven patients were identified (55% men) with mean age 39 years (range 21-63). Four had a prior history of systemic sarcoidosis leading to earlier diagnosis (6.7 vs 13.1 months). Six were found to have evidence of systemic sarcoidosis on further investigation and one was biopsy proven isolated neurosarcoidosis. The commonest site of CNS involvement was the cranial nerves (64%), and headache (45%) was the most frequent presenting symptom. MRI abnormalities included leptomeningeal enhancement, white matter lesions, acute arteritis, spinal cord lesion, and cauda equina enhancement. The commonest CSF finding was raised protein (n = 6) and a lymphocytic pleocytosis (n = 7). Serum ACE was only elevated in three cases. Ten patients were treated with both corticosteroids and steroid-sparing agents 8 of whom went into remission. CONCLUSIONS: This series highlights the diverse nature of neurosarcoidosis. Early introduction of aggressive therapy with corticosteroids and steroid-sparing agents appears to improve clinical outcome.