Rectifying global inequities in neuromyelitis optica diagnosis and treatment.

The standard of care for patients with neuromyelitis optica (NMO) has become highly unequal globally. Sufficient data have been published to demonstrate that NMO is a disabling-and at times, fatal-disease needing preventive immunosuppressive treatment. Since 2019, there are multiple regulatory authority-approved disease-modifying therapies (DMTs) for aquaporin-4 antibody seropositive NMO for patients. Reframing the picture of NMO globally is now needed. When considered as a disease of high mortality when left untreated, parallel programs to those for cancer, HIV/AIDS, or tuberculosis can be considered. Nine collective goals for rectifying global inequities in NMO diagnosis and treatment are proposed.

How Should Relief Organizations Fund Care of Patient-Asylees Who Have Cancer?

Several clinical and ethical dilemmas arise when caring for refugees with complex, costly, and chronic conditions in low- and middle-income countries where they often first seek asylum. This commentary responds to a case involving a patient asylee with a malignant brain tumor and considers these questions: (1) Should refugee care costs be allocated as a specific amount per refugee or designated to fund only specific interventions? (2) Should interventions not available to host population members with low incomes be available to refugees? (3) Should refugee cancer care focus on cure, rehabilitation, and palliation or on just one or two of these areas? This commentary responds to these questions by considering how to approach trade-offs between numbers of patients treated and per patient expenditures.

Disease modifying therapy management of multiple sclerosis after stem cell therapies: A retrospective case series.

BACKGROUND: Stem cell therapies (SCT) have not received formal regulatory approval for the treatment of people with multiple sclerosis (PwMS), but PwMS may seek various options on their own accord. The current literature largely focuses on the efficacy and safety of SCT in PwMS in clinical trials, in particular autologous hematopoietic stem cell transplantation (aHSCT), in carefully selected participants. There is little reported on the MS disease modifying therapy (DMT) management of PwMS who choose to undergo SCT outside of these trials. METHODS: We identified PwMS from two academic centers who had MS diagnosis fulfilling 2017 McDonald criteria and received SCT (methodologies permitted: aHSCT, umbilical-derived mesenchymal stem cells and/or adipose-derived mesenchymal stem cells (AdMSC)), with the goal to treat MS, between 1/1/2015 and 11/30/2021. RESULTS: Nine PwMS (five females; age range at SCT treatment 25-69 years old; MS disease duration 1-12 years; six relapsing-remitting, three secondary progressive, one primary progressive) underwent a total of eleven SCTs (nine aHSCT, two AdMSC, one umbilical-derived MSC) with the goal to treat MS. Two of six PwMS who underwent SCT <10 years from MS diagnosis, and one of three PwMS who underwent stem cell therapies >10 years from MS diagnosis were clinically stable thereafter. An MS DMT was resumed in five PwMS afterwards, including rituximab, ocrelizumab, siponimod, and glatiramer acetate: one remained clinically stable, whereas four clinically progressed. Four PwMS remained off of a DMT: three were clinically stable, whereas one clinically progressed. All nine patients demonstrated radiographic stability by MRI after SCT. Only one met formal criteria to consider aHSCT for MS. CONCLUSIONS: We demonstrate the heterogeneous real-world experience of treating MS after patient-chosen experimental SCTs, detailing the range of DMT management in various patient circumstances. Limitations of our study include its small sample size and the variety of stem cell therapies received.

A point-of-care diagnostic test for aquaporin-4 antibody seropositive neuromyelitis optica.

BACKGROUND: Given the need for specialized laboratory techniques, diagnostic testing for serum antibodies to aquaporin-4, a protein associated with neuromyelitis optica spectrum disorder (NMOSD), is not globally accessible. We aimed to evaluate a novel point-of-care, filter paper-based test for serum AQP4 antibodies (AQP4-Ab). METHODS: Adults with AQP4-Ab seropositive NMOSD and seronegative controls (with other central nervous system demyelinating diagnoses) used lancets to place blood drops (∼1 mL) on filter paper cards. Samples were analyzed after an average of 9.4 days using transfected AQP4-GFP HEK293 cells, and results were compared to participants' prior serum AQP4-Ab test results by blinded laboratory staff. RESULTS: Of 40 participants (mean age 53.7 years; 83% female), 25 were cases and 15 were controls. The most common diagnosis of controls was multiple sclerosis (73%). The average NMOSD disease duration was 6.3 years. All AQP4-Ab seropositive participants were on disease modifying therapies at the time of participation. The point-of-care test yielded a sensitivity of 80% and specificity of 93% (positive and negative predictive values 95% and 74%). CONCLUSION: This point-of-care AQP4-Ab testing method may become a pragmatic option to diagnose AQP4-Ab seropositive NMOSD in difficult-to-reach settings. This method should be confirmed with other testing parameters and field tested in new populations.

Measuring Ambulation, Motor, and Behavioral Outcomes with Post-stroke Fluoxetine in Tanzania: The Phase II MAMBO Trial.

We test the safety of fluoxetine post-ischemic stroke in sub-Saharan Africa. Adults with acute ischemic stroke, seen <14 days since new-onset motor deficits, were enrolled from November 2019 to October 2020 in a single-arm, open-label phase II trial of daily fluoxetine 20 mg for 90 days at Muhimbili National Hospital, Dar es Salaam, Tanzania. The primary outcome was safety with secondary outcomes of medication adherence and tolerability. Thirty-four patients were enrolled (11 were female; mean age 52.2 years, 65% < 60 years old; mean 3.3 days since symptom onset). Participants had hypertension (74%), diabetes (18%), and smoked cigarettes (18%). The median National Institutes of Health Stroke Scale score at enrollment was 10.5. The median Fugl-Meyer Motor Scale score was 28.5 (upper extremity 8, lower extremity 17.5). 32/34 participants (91%) survived to 90 days. There were eight serious and two nonserious adverse events. Deaths occurred due to gastrointestinal illness with low serum sodium (nadir 120 mmol/L) with seizure and gastrointestinal bleed from gastric cancer. The average sodium level at 90 days was 139 mmol/L (range 133-146) and alanine transaminase was 28 U/L (range 10-134). Fluoxetine adherence was 96%. The median modified Rankin Scale score among survivors at 90 days was 2 and Fugl-Meyer Motor Scale score was 66 (upper extremity 40, lower extremity 27). Median 90-day Patient Health Questionnaire-9 and Montgomery-Åsberg scores were 3.5 and 4 (minimal depression). Fluoxetine administration for 90 days poststroke in sub-Saharan Africa was generally safe and well-tolerated, but comorbid illness presentations were fatal in 2/34 cases, even after careful participant selection.

CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study.

OBJECTIVE: To study long-term outcomes in patients with CNS demyelinating events exposed to TNFa-inhibitors (TNFai), including subsequent clinical relapse, MRI lesions, and use of disease modifying therapy (DMT) for MS. METHODS: Adult patients evaluated for a CNS demyelinating disease during TNFai use were identified at Mass General Brigham [01/1998-08/2020] and analyzed in clinically-relevant subgroups. Inclusion criteria required a first neurological event while taking a TNFai, MRI lesions consistent with demyelination, and the absence of a more probable alternative diagnosis. RESULTS: 21 cases (mean age 44 years, 20 female, 14 ≥ 2 MS risk factors) had an index neurological event (INE) at a median of 12 months (range 1-176) from onset of TNFai use (adalimumab in 10, etanercept 6, infliximab 5). MRI lesions were most often present in periventricular (16/20, 80%) and spinal zones (10/20, 50%); 37% (7/19) met ≥ 2 Barkhof criteria at onset. CSF testing was abnormal in 64% (7/11). 67% (10/15) with available follow-up MRIs developed new lesions by a median of 29.5 months of MRI surveillance (median MRI surveillance 60 months); 55% (11/20) met ≥ 2 Barkhof criteria. 47% (8/17) suffered a clinical relapse by a median of 40.5 months of clinic follow-up (median clinic follow-up since INE: 26 months). In patients discontinuing TNFai (18/21, 86%) at INE onset, 56% (10/18) had further evidence of CNS demyelination. Six patients (6/21, 29%) started an MS disease modifying therapy (DMT) at INE of whom 50% (3/6) had subsequent disease activity. Continuing or restarting TNFai was followed by relapse in 75% (3/4). 65% (13/20) met 2017 McDonald criteria for MS at INE with another 10% (15/20, 75%) by study conclusion. CONCLUSIONS: With extended follow-up, a majority of patients had a relapsing CNS demyelinating disorder-as evidenced by new MRI lesions or clinical relapses-despite TNFai discontinuation.

Central nervous system disease with JC virus infection in adults with congenital HIV.

OBJECTIVE: The aim of this study was to describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS). METHODS: We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centres in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, cerebrospinal fluid (CSF) analyses, radiographic features, modified Rankin Scale (mRS) scores and survival were collected from the electronic medical record up to a censoring date of 1 August 2020. RESULTS: Among 10 adults with congenitally acquired HIV, nine were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for six patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for three individuals, and approximately 2 years for the remaining two. CONCLUSION: Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals.

Urinary Arsenic and Cadmium Associations with Findings from Cranial MRI in American Indians: Data from the Strong Heart Study.

BACKGROUND: Arsenic and cadmium are known cardiovascular toxicants that pose disproportionate risk to rural communities where environmental exposures are high. American Indians have high vascular risk, which may be attributable in part to these exposures. OBJECTIVE: We examined urine metal concentrations in association with magnetic resonance imaging findings of vascular brain injury or cerebral atrophy in adult American Indians. METHODS: We measured arsenic and cadmium in American Indian participants from the Strong Heart Study (1989-1991) and evaluated these associations with later (2010-2013) measures of infarct, hemorrhage, white matter hyperintensity (WMH) grade, brain and hippocampal volume, and sulcal and ventricle atrophy using nested multivariate regression analyses. RESULTS: Among participants with available data (N=687), the median urine arsenic:creatinine ratio was 7.54µg/g [interquartile range (IQR): 4.90-11.93] and the cadmium:creatinine ratio was 0.96µg/g (IQR: 0.61-1.51). Median time between metal measurement and brain imaging was 21 y (range: 18-25 y). Statistical models detected significant associations between arsenic and higher burden of WMH [grade increase=0.014 (95% CI: 0.000, 0.028) per 10% increase in arsenic]; and between cadmium and presence of lacunar infarcts [relative risk (RR)=1.024 (95% CI: 1.004, 1.045) per 10% increase in cadmium]. DISCUSSION: This population-based cohort of American Indian elders had measured values of urine arsenic and cadmium several times higher than previous population- and clinic-based studies in the United States and Mexico, and comparable values with European industrial workers. Our findings of associations for arsenic and cadmium exposures with vascular brain injury are consistent with established literature. Environmental toxicant accumulation is modifiable; public health policy may benefit from focusing on reductions in environmental metals. https://doi.org/10.1289/EHP6930.

Cancer in Syrian refugees in Jordan and Lebanon between 2015 and 2017.

Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010-12) and Syria (2009-11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015-17) and Jordan (2016-17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers.

Missed opportunities for epilepsy surgery referrals in Bhutan: A cohort study.

OBJECTIVE: To quantify the missed opportunities for epilepsy surgery referral and operationalize the Canadian Appropriateness of Epilepsy Surgery (CASES) tool for use in a lower income country without neurologists. METHODS: People with epilepsy were recruited from the Jigme Dorji Wangchuck National Referral Hospital from 2014-2016. Each participant was clinically evaluated, underwent at least one standard EEG, and was invited to undergo a free 1.5 T brain MRI. Clinical variables required for CASES were operationalized for use in lower-income populations and entered into the free, anonymous website tool. FINDINGS: There were 209 eligible participants (mean age 28.4 years, 56 % female, 179 with brain MRI data). Of the 179 participants with brain MRI, 43 (24.0 %) were appropriate for an epilepsy surgery referral, 21 (11.7 %) were uncertain, and 115 (64.3 %) were inappropriate for referral. Among the 43 appropriate referral cases, 36 (83.7 %) were "very high" and 7 (16.3 %) were "high" priorities for referral. For every unit increase in surgical appropriateness, quality of life (QoL) dropped by 2.3 points (p-value <0.001). Among the 68 patients who took >1 antiepileptic drug prior to enrollment, 42 (61.8 %) were appropriate referrals, 14 (20.6 %) were uncertain, and 12 (17.6 %) were inappropriate. CONCLUSION: Approximately a quarter of Bhutanese epilepsy patients who completed evaluation in this national referral-based hospital should have been evaluated for epilepsy surgery, sometimes urgently. Surgical services for epilepsy are an emerging priority for improving global epilepsy care and should be scaled up through international partnerships and clinician support algorithms like CASES to avoid missed opportunities.

Progressive multifocal leukoencephalopathy: A 25-year retrospective cohort study.

OBJECTIVE: To characterize the risk factors, clinical course, and treatment of patients with progressive multifocal leukoencephalopathy (PML) diagnosed and followed over a 25-year epoch at 2 academic hospitals. METHODS: Patients with a definite diagnosis of PML were identified by positive CSF PCR for JC virus or histopathology between January 1, 1994, and January 1, 2019. Demographic and PML-specific variables were recorded on symptomatic presentation and at follow-up, including risk factors, clinical outcome, neuroimaging findings, and modified Rankin Scale (mRS) score at last follow-up. RESULTS: There were 91 patients with confirmed PML. HIV infection was the most common risk factor, identified in 49% (n = 45). Other frequent risk factors included lymphoma, leukemia, or myelodysplasia, identified in 31% of patients (n = 28); exposure to chemotherapeutic medications (30%, n = 27); and exposure to monoclonal antibody therapies (19%, n = 17). Thirty percent of the cohort was alive at the time of censoring, with a median mRS of 2 points, indicating slight disability at last follow-up. Median survival following PML diagnosis in HIV-infected patients was longer than in HIV-uninfected patients (1,992 vs 101 days, p = 0.024). Forty patients survived more than 1 year after PML symptom onset, of whom 24 were HIV infected (60%). Thirteen patients survived more than 10 years after PML symptom onset, all HIV infected, of the 59 patients diagnosed before June 1, 2009, and eligible for 10-year survivor status (22%). CONCLUSIONS: We add to the limited literature on PML by reporting its epidemiology in a large observational cohort. These parameters may be useful for future clinical trials that measure survival and clinical outcomes.

Yield of Brain MRI in Clinically Diagnosed Epilepsy in the Kingdom of Bhutan: A Prospective Study.

BACKGROUND: People with epilepsy (PWE) in low- and middle-income countries may not access the health resources that are considered optimal for epilepsy diagnosis. The diagnostic yield of magnetic resonance imaging (MRI) has not been well studied in these settings. OBJECTIVES: To report the diagnostic yield of brain MRI and identify clinical associations of abnormal MRI findings among PWE in a neurocysticercosis-endemic, resource-limited setting and to identify the proportion and putative structural brain causes of drug-resistant epilepsy. METHODS: PWE were prospectively enrolled at the Jigme Dorji Wangchuck National Referral Hospital in Bhutan (2014-2015). Each participant completed clinical questionnaires and a 1.5-Tesla brain MRI. Each MRI was reviewed by at least 1 radiologist and neurologist in Bhutan and the United States. A working definition of drug-resistant epilepsy for resource-limited settings was given as (a) seizures for >1 year, (b) at least 1 seizure in the prior year, and (c) presently taking 2 or more antiepileptic drugs (AEDs). Logistic regression models were constructed to test the cross-sectional association of an abnormal brain MRI with clinical variables. FINDINGS: A total of 217 participants (125 [57%] female; 54 [25%] < 18 years old; 199 [92%] taking AEDs; 154 [71%] with a seizure in the prior year) were enrolled. There was a high prevalence of abnormal brain MRIs (176/217, 81%). Mesial temporal sclerosis was the most common finding (n = 115, 53%, including 24 children), exceeding the number of PWE with neurocysticercosis (n = 26, 12%, including 1 child) and congenital/perinatal abnormalities (n = 29, 14%, including 14 children). The number of AEDs (odds ratio = .59, P = .03) and duration of epilepsy (odds ratio = 1.11, P = .02) were significantly associated with an abnormal MRI. Seizure in the prior month was associated with the presence of mesial temporal sclerosis (odds ratio = .47, P = .01). A total of 25 (12%) participants met our definition of drug-resistant epilepsy, with mesial temporal sclerosis (n = 10), congenital malformations (n = 5), and neurocysticercosis (n = 4) being the more common findings. CONCLUSIONS: The prevalence of abnormalities on brain MRI for PWE in resource-limited settings is high as a result of a diffuse range of etiologies, most commonly mesial temporal sclerosis. Drug-resistant epilepsy accounted for 12% of the referral population in a conservative estimation.

Neurocysticercosis in Bhutan: a cross-sectional study in people with epilepsy.

BACKGROUND: We sought to provide an assessment of the burden of neurocysticercosis among people with epilepsy (PWE) in Bhutan and evaluate the yield of various tests for Taenia solium. METHODS: PWE were enrolled at the National Referral Hospital in Thimphu (2014-2015). Serum was tested for anti-Taenia solium IgG using ELISA (Ab-ELISA), enzyme-linked immunoelectrotransfer blot (EITB), and parasite antigen. Results were compared to brain MRI. Participants were categorized as definite neurocysticercosis (MRI and EITB positive), probable neurocysticercosis (MRI or EITB positive), or without neurocysticercosis. Logistic regression models were constructed to explore clinicodemographic associations. RESULTS: There were 12/205 (6%, 95% CI 2%, 9%) definite and 40/205 (20%, 95% CI 14%, 25%) probable neurocysticercosis cases. 25/205 (12%) with positive EITB did not have neurocysticercosis on MRI, and 15/205 (7%) participants with positive MRI had negative EITB. Participants with neurocysticercosis-suggestive lesions on MRI had an average of 1.2 cysts (parenchymal 26/27; nodular/calcified stage 21/27). In a multivariable analysis, present age (OR 1.05, 95% CI 1.01,1.09, p=0.025) was positively associated with (combined probable or definite) neurocysticercosis while mesial temporal sclerosis on MRI (OR 0.294, 95% CI 0.144, 0.598, p=0.001) was negatively associated. CONCLUSIONS: Neurocysticercosis was associated with 6-25% of epilepsy in a Bhutanese cohort. Combining EITB and MRI would aid the diagnosis of neurocysticercosis among PWE since no test identified all cases.

Stroke in HIV-infected African Americans: a retrospective cohort study.

The risk of having a first stroke is nearly twice as high among African Americans compared to Caucasians. HIV/AIDS is an independent risk factor for stroke. Our study aimed to report the risk factors and short-term clinical outcomes of African Americans with HIV infection and new-onset stroke admitted at the Johns Hopkins Hospitals (2000-2012). Multivariate linear regression was used to examine the association between potential predictors and odds of an unfavorable outcome, defined as a higher modified Rankin Scale (mRS) score on hospital discharge. African Americans comprised 105/125 (84%) of HIV-infected new-onset stroke inpatients (median age 50 years; 69% men; median CD4 140/mL; ischemic 77%; 39% taking highly active antiretroviral therapy). Vascular risk factors were common: hypertension (67%), cigarette smoking (66%), dyslipidemia (42%), hepatitis C (48%), intravenous drug abuse (32%), and prior myocardial infarction (29%). Prior aspirin and statin use were uncommon (18%, 9%). Unfavorable outcome (mRS score 4-6, n = 22 of 90 available records) was noted in 24% of patients, including seven in-hospital deaths. On multivariate analyses, higher CD4 count on hospital admission was associated with a lower mRS (-0.2 mRS points per 1 unit increase in CD4, 95% CI (-0.3, 0), p = 0.03). Intracerebral hemorrhage was also associated with a lower mRS (1.0 points lower, 95% CI (0.2, 1.8) compared to ischemic stroke, p = 0.01) after adjustment for other potential predictors. This underscores the importance of HIV infection on functional stroke outcomes beyond its recognized influence on stroke risk.

Neuropsychiatric disorders among Syrian and Iraqi refugees in Jordan: a retrospective cohort study 2012-2013.

BACKGROUND: The burden of neuropsychiatric disorders in refugees is likely high, but little has been reported on the neuropsychiatric disorders that affect Syrian and Iraqi refugees in a country of first asylum. This analysis aimed to study the cost and burden of neuropsychiatric disorders among refugees from Syria and Iraq requiring exceptional, United Nations-funded care in a country of first asylum. METHODS: The United Nations High Commissioner for Refugees works with multi-disciplinary, in-country exceptional care committees to review refugees' applications for emergency or exceptional medical care. Neuropsychiatric diagnoses among refugee applicants were identified through a retrospective review of applications to the Jordanian Exceptional Care Committee (2012-2013). Diagnoses were made using International Classification of Disease-10(th) edition codes rendered by treating physicians. RESULTS: Neuropsychiatric applications accounted for 11% (264/2526) of all Exceptional Care Committee applications, representing 223 refugees (40% female; median age 35 years; 57% Syrian, 36% Iraqi, 7% other countries of origin). Two-thirds of neuropsychiatric cases were for emergency care. The total amount requested for neuropsychiatric disorders was 925,674 USD. Syrian refugees were significantly more likely to request neurotrauma care than Iraqis (18/128 vs. 3/80, p = 0.03). The most expensive care per person was for brain tumor (7,905 USD), multiple sclerosis (7,502 USD), and nervous system trauma (6,466 USD), although stroke was the most frequent diagnosis. Schizophrenia was the most costly and frequent diagnosis among the psychiatric disorders (2,269 USD per person, 27,226 USD total). CONCLUSIONS: Neuropsychiatric disorders, including those traditionally considered outside the purview of refugee health, are an important burden to health among Iraqi and Syrian refugees. Possible interventions could include stroke risk factor reduction and targeted medication donations for multiple sclerosis, epilepsy, and schizophrenia.

Neurologic manifestations of the neglected tropical diseases.

BACKGROUND: The World Health Organization has identified 17 neglected tropical diseases (NTDs) that disproportionately affect the world's poorest populations. The neurologic aspects of many of these NTDs have received relatively little attention. METHODS: A review was performed in PubMed (MedLine) for each NTD by disease name, name of its causative organism, and neurology, neurosurgery, neurologist, brain, spinal cord, peripheral nerve, muscle, nervous system, encephalitis, meningitis, encephalopathy, stroke, neuropathy, and myopathy (1968-Sept. 2013). The Oxford Center for Evidence-based Medicine guidelines were used to determine the level of evidence of neurological involvement and treatment based on the reports identified. RESULTS: Neurologic manifestations were reported for all NTDs except yaws. Neurologic involvement was described in systematic reviews for four NTDs (Chagas disease, echinococcosis, rabies, cysticercosis) (levels 2a-3a), retrospective cohort studies for six (dengue, human African trypanosomiasis, leishmaniasis, leprosy, onchocerciasis, schistosomiasis) (levels 2b-3b), case series for one (foodborne trematodiasis) (level 4), and case reports for five (Buruli ulcer, dracunculiasis, filariasis, soil-transmitted helminthes, and trachoma). Level 1 evidence for treatment of neurologic manifestations of NTDs was found for human African trypanosomiasis, leprosy, and cysticercosis and level 2 evidence exists for treatment of neurologic involvement in Chagas disease. For the remaining NTDs, treatment of neurologic complications is described in case series and case reports only. CONCLUSIONS: Neurologic manifestations of NTDs cause significant morbidity and mortality, although limited evidence exists on how best to treat these neurologic complications. Increased awareness of neurologic manifestations of the NTDs can increase their early identification and treatment, contributing to ongoing elimination and eradication campaigns.

Cancer in refugees in Jordan and Syria between 2009 and 2012: challenges and the way forward in humanitarian emergencies.

Treatment of non-communicable diseases such as cancer in refugees is neglected in low-income and middle-income countries, but is of increasing importance because the number of refugees is growing. The UNHCR, through exceptional care committees (ECCs), has developed standard operating procedures to address expensive medical treatment for refugees in host countries, to decide on eligibility and amount of payment. We present data from funding applications for cancer treatments for refugees in Jordan between 2010 and 2012, and in Syria between 2009 and 2011. Cancer in refugees causes a substantial burden on the health systems of the host countries. Recommendations to improve prevention and treatment include improvement of health systems through standard operating procedures and innovative financing schemes, balance of primary and emergency care with expensive referral care, development of electronic cancer registries, and securement of sustainable funding sources. Analysis of cancer care in low-income refugee settings, particularly in sub-Saharan Africa, is needed to inform future responses.

Night-shift work and risk of breast cancer: a systematic review and meta-analysis.

A 2007 report by the International Agency for Research on Cancer classified night-shift work as possibly carcinogenic to humans, emphasizing, in particular, its association with breast cancer. Since this report and the publication of the last systematic review on this topic, several new studies have examined this association. Hence, to provide a comprehensive update on this topic, we performed a systematic review and meta-analysis. We searched Medline, Embase, CINAHL, Web of Science (Conference Proceedings), and ProQuest dissertations for studies published before March 1, 2012, along with a manual search of articles that cited or referenced the included studies. Included were observational case-control or cohort studies examining the association between night-shift work and breast carcinogenesis in women, which all ascertained and quantified night-shift work exposure. The search yielded 15 eligible studies for inclusion in the systematic review and meta-analysis. Using random-effects models, the pooled relative risk (RR) and 95 % confidence intervals (CIs) of breast cancer for individuals with ever night-shift work exposure was 1.21 (95 % CI, 1.00-1.47, p = 0.056, I (2) = 76 %), for short-term night-shift workers (<8 years) was 1.13 (95 % CI, 0.97-1.32, p = 0.11, I (2) = 79 %), and for long-term night-shift workers (≥8 years) was 1.04 (95 % CI, 0.92-1.18, p = 0.51, I (2) = 55 %), with substantial between-study heterogeneity observed in all analyses. Subgroup analyses suggested that flight attendants with international or overnight work exposure and nurses working night-shifts long-term were at increased risk of breast cancer, however, these findings were limited by unmeasured confounding. Overall, given substantial heterogeneity observed between studies in this meta-analysis, we conclude there is weak evidence to support previous reports that night-shift work is associated with increased breast cancer risk.

The Melkersson-Rosenthal syndrome: a retrospective study of biopsied cases.

Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis. Large case series including treatment are limited. A retrospective records review was performed for the diagnoses Melkersson-Rosenthal syndrome, granulomatous cheilitis, and orofacial granulomatosis, confirmed by noncaseating granulomas on biopsy, at the Mayo Clinic in Rochester, Minnesota (1979-2009). There were 72 patients [51 women (71 %), mean age at presentation 39 years (range 8-79)] identified with facial edema with noncaseating granulomas on skin biopsy. Lingua plicata occurred in 34 cases (47 %, 95 % confidence interval 35.3-59.3 %). Unilateral or partial facial nerve palsy occurred in 14 cases (19.4, 95 % confidence interval 11.4-30.8 %). Comorbidities among those with facial edema included periodontal disease (n = 10, 14 %), history of allergic disease (n = 10, 14 %), Crohn's Disease (n = 6, 8 %), migraine headaches (n = 5, 7 %), and systemic lupus erythematosus (n = 2, 3 %). There were no patients who had low C1q or C4 levels among those who were tested. Overall, the full triad canonical of Melkersson-Rosenthal syndrome was observed in nine patients (seven female, median age at symptomatic presentation 35 years (range 10-74 years), 13 %, (95 % confidence interval 6.2-22.9 %) with a median time from first symptoms to diagnosis of 4 years (range 1-35). The medication treatments attempted in the nine patients with the full triad of symptoms included non-steroidal anti-inflammatory drugs, oral and intra-lesional steroids, metronidazole, dapsone, acyclovir, methotrexate, and thalidomide with no consistent treatment responses. The Melkersson-Rosenthal syndrome may present over the course of most of the lifespan and may require several years of observation to be diagnosed. Neurologists who observe a combination of facial edema and facial palsy in a patient should consider the diagnosis of MRS and proceed to a diagnostic skin biopsy and a trial of steroid treatment for their patient.

Causes and outcomes of persistent vegetative state in a Chinese versus American referral hospital.

OBJECTIVE: To compare the etiologies and clinical outcomes of patients in a persistent vegetative state (PVS) between a Chinese and US referral hospital. METHODS: A retrospective, observational study at the Peking Union Medical College Hospital, Beijing, China and Johns Hopkins Hospital, Baltimore, USA (2001-2010) was performed. RESULTS: There were 36 cases of PVS diagnosed. In Beijing, there were 19 cases: mean age 57 years, range 3-86, (42 %) female, with 37 % of patients observed to survive more than 1 year (range >1 month to >28 years, median >6 months). Causes of PVS in Beijing were hemorrhagic stroke (n = 4, 21 %), ischemic stroke (n = 2, 11 %), cardiac arrest (n = 5, 26 %, including 4 with attempted cardiopulmonary resuscitation (CPR)), traumatic brain injury (n = 3, 16 %), and one each of mitochondrial encephalomyopathy, acute disseminated encephalomyelitis, Lennox Gastaut Syndrome, and epilepsy with craniopharyngioma (n = 4, 21 %). In Baltimore, there were 17 cases of PVS: mean age 43 years, range 15-83, 59 % female, with 41 % observed to survive more than 1 year (range >1 month to >10 years, median >3 years). Causes of PVS in Baltimore were ischemic stroke (n = 3, 18 %), cardiac arrest (n = 3, 18 %, including one with attempted CPR), traumatic brain injury (n = 3, 18 %), neurodegenerative conditions (n = 2, 12 %), and hypoxic ischemic encephalopathy due to respiratory arrest (n = 3, 18 %), metabolic derangements (n = 2, 12 %), and meningitis (n = 1, 6 %). CONCLUSIONS: There may be a long survival period for patients with PVS, including in China where resource constraints exist for acute neurologic care. Stroke appears to be the most common underlying cause of PVS in Chinese patients, followed closely by cardiac arrest with attempted CPR. There appear to be more varied causes of PVS in the US referral hospital with a predominance of stroke, cardiac arrest, and traumatic brain injury.