Differential expression of miRNA 155 and miRNA 146a in Parkinson's disease patients

Elisa Caggiu, Kai Paulus, Giuseppe Mameli, Giannina Arru, ... Leonardo A. Sechi

• Pages 1-4
• https://doi.org/10.1016/j.ensci.2018.09.002
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• Abstract

  Parkinson's disease is a neurodegenerative disorder and its etiology is unknown, numerous studies show how different environmental factors can influence the development of disease. miRNAs are involved in several pathologies and their dysregulation contribute to different pathologies, also in neurodegenerative such as Parkinson's disease, Alzheimer's disease, Huntington's disease and Amyotrophic lateral sclerosis. In this study, we profiled the expression of different candidate miRNAs: miR-155, miR-26a, miR-146a, and miR132, in PBMCs of L-dopa treated Parkinson patients and unaffected controls (HCs).We investigated the expression of miRNAs by RT-real time PCR, the results were subjected to statistical analysis. miRNA-155-5p was generally up-regulated in PD patients compared to HCs whereas miRNA-146a-5p was down-regulated in PD patients in comparison to HCs. It is interesting to point out that the expression of miR-155-5p was modified by levodopa treatment, in fact a down-regulation of miR-155-5p in PD patients with the highest dosage was observed.

  In conclusion, miRNA 155 could not only be a promising target for the anti-inflammatory therapy in PD but also a good candidate as a disease progression biomarker. The role of levodopa in modulating the levels of miRNA 155 requires further studies.

Reversible istradefylline-induced pleurothotonus in a patient with Parkinson's disease: A case report and literature review

Yuzuru Yasuda

• Pages 5-7
• https://doi.org/10.1016/j.ensci.2018.09.001
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• Abstract

  Pleurothotonus, commonly known as Pisa syndrome (PS), is characterized by abnormal lateral flexion of the trunk. The precise mechanism of this disease is unknown. Istradefylline was administered to a 68-year-old male patient with Parkinson's disease (PD) to treat wearing-off; however, PS appeared 4 months after the first istradefylline treatment. Despite drug adjustments for 9 months, no improvement was observed. Finally, istradefylline was discontinued, and PS symptoms gradually improved over the subsequent 4 months and eventually disappeared. From 2005 to 2014, six studies appeared in the literature on dopaminergic therapy for PS patients with PD. The period between PS appearance after drug introduction until PS recovery with appropriate treatment differs among drugs. This study aimed to identify the drugs that initiate PS and assess the period between PS appearance and disappearance, respectively, after the drug is first administered and later discontinued.

Pharmacokinetics and safety/efficacy of levodopa pro-drug ONO-2160/carbidopa for Parkinson's disease

Masahiro Nomoto, Masahiro Nagai, Noriko Nishikawa, Rina Ando, ... Atsushi Takeda

• Pages 8-13
• https://doi.org/10.1016/j.ensci.2018.09.003
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• Abstract

  We conducted a phase I study investigating the efficacy, safety, and tolerability of ONO-2160, a newly developed levodopa pro-drug, and carbidopa compared with levodopa and carbidopa to stabilize levodopa plasma concentration fluctuations in Japanese patients with Parkinson's disease. In an open-label two-period design, patients (n = 12) with Parkinson's disease received levodopa and carbidopa for 3 days before 7 days of treatment with ONO-2160 and carbidopa. Patients were primarily evaluated using the Unified Parkinson's Disease Rating Scale Part III, a Parkinson's disease symptom diary, and analysis of adverse events. Pharmacokinetic analysis of plasma levodopa concentration was also performed.

  ONO-2160 and carbidopa therapy stabilized effective plasma levodopa concentration. No adverse events with safety concerns were observed. The combination of ONO-2160 and carbidopa produced a prolonged and stable plasma levodopa concentration with a reduction in Unified Parkinson's Disease Rating Scale Part III total scores. The combination was well tolerated, with no safety concerns, when administered to Japanese patients with Parkinson's disease.

Ischemic stroke as initial manifestation of systemic lupus erythematosus: A case report and review of the literature

Stefanos Ioannidis, Michael Mavridis, Panayiotis D. Mitsias

• Pages 26-30
• https://doi.org/10.1016/j.ensci.2018.11.001
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• Abstract

  Stroke is a frequent occurrence among patients suffering from systemic lupus erythematosus (SLE), but it rarely occurs as the initial manifestation of the disease. We here present the case of a 37 year-old patient who developed an acute cerebellar ischemic stroke as initial event of SLE: elevated partial thromboplastin time and ESR, thrombocytopenia, anti-ds-DNA, anti-SSA, anti-JO-1, and the lupus anticoagulant were detected, and the diagnosis of SLE was established. In addition, we reviewed the literature in order to clarify the demographic, clinical, imaging and outcome characteristics of such a presentation, and found 10 similar cases. Most patients were young (age 31.7 ± 8.5 years) and women (8/11, 72.7%). Stroke most often affected the vertebrobasilar territory (7/11, 63.6%). The stroke mechanism was not clearly defined in these cases. Treatment with immunosuppression and anticoagulation was considered to be a reasonable choice for early secondary stroke prevention. The occurrence of ischemic stroke, primarily in the vertebrobasilar system among young patients, especially women, should always raise suspicion for underlying SLE, and prompt diagnostic investigations to confirm or exclude its presence.

Stroke in the Arab World: A bibliometric analysis of research activity (2002–2016)

Hamza A. Salhab, Pascale Salameh, Hind Hajj, Hassan Hosseini

• Pages 40-45
• https://doi.org/10.1016/j.ensci.2018.11.010
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• Abstract

  Background

  The Arab world has an increasing prevalence of strokes, a leading cause of death in this part of the world.

  Aims

  The aim of this article is to quantify the stroke research activity in the Arab countries over the past 15 years taking into consideration the population, GDP, and DALY of each country.

  Methods

  A PubMed search was conducted to find stroke research articles published from the Arab countries between 2002 and 2016 (inclusive). Medical subject headings related to strokes and author origin/affiliation were used for this purpose.

  Results

  The Arab world only produced 0.51% of all the stroke-related publications on PubMed even though the stroke-related DALY percentage in this region was greater than 2.88% during the period we studied. In general, the number of publications increased in the last few years. Somalia came first regarding the percentage of stroke to non-stroke publications released. Lebanon had the highest number of publications per GDP (in US Billion Dollars), Qatar had the highest number of publications per million persons (PPMP), while Saudi Arabia had the highest number of publications per 1% of stroke DALY. In addition, a strong positive correlation was found between the number of stroke publications and GDP; however, the correlation between the number of stroke publication and either population size or DALY was a weak positive one.

  Conclusions

  A general increase in publications is noticed, but stroke research activity in the Arab world is still poor compared to other parts of the world.

Recurrent thrombolysis of a stuttering lacunar infarction captured on serial MRIs

Imama Naqvi, Alexis N. Simpkins, Kaylie Cullison, Emily Elliott, ... John K. Lynch

• Pages 14-17
• https://doi.org/10.1016/j.ensci.2018.10.001
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• Abstract

  Lacunar strokes account for about a fourth of all ischemic strokes. Pontine infarcts often present with stuttering symptoms, referred to as pontine warning syndrome (PWS). Patients presenting with fluctuating symptoms can appear to have rapidly improving symptoms and thus often go untreated despite the risk of recurrent deficits. MRI carries a higher sensitivity in detecting posterior circulation strokes compared to computed topagraphy, but does not always indicate irreversible injury. Here we present the first description of a stuttering lacune, captured radiographically on serial magnetic resonance imaging (MRI), that was initially averted with the administration of intravenous (IV) tissue plasminogen activator (tPA), only to return a month later and progress on imaging despite re-administration of tPA. During the first admission, our patient had spontaneous resolution of symptoms with complete reversal on restricted diffusion soon after IV tPA administration. On the second admission, the stuttering symptoms returned as did the same pontine lesion. Although his stuttering lesions lasted for several days, and the pontine lesion did ultimately progress to partial infarction on MRI, he was discharged home without neurologic deficits. Our case suggests that tPA may be of benefit in patients with lacunar pontine strokes even if symptoms rapidly improve or resolve.

Pseudotumor cerebri and lung cancer-associated jugular vein thrombosis: Role of anatomical variations of torcular herophili

Wakoto Matsuda, Shozo Noguchi, Fumino Fujiyama

• Pages 18-20
• https://doi.org/10.1016/j.ensci.2018.11.002
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• Abstract

  A 71-year-old male appeared at the facility complaining of disturbance of consciousness and bilateral papilledema. The laboratory test revealed anemia and coagulation abnormality. A physical examination and magnetic resonance imaging (MRI) of the brain with and without gadolinium showed no abnormalities. A lumbar puncture showed a high pressure, but a normal cerebrospinal fluid (CSF) cell count. Cerebral angiography showed no morphological abnormalities, but it revealed an asymmetric right dominant type of confluence of the sinuses with the partially-communicating left transverse sinus in the late phase. Furthermore, there was a delay in the cerebral circulation time (CCT). Subsequently, venography and ultrasonography revealed right internal jugular vein thrombosis associated with lung cancer. The patient recovered from the disturbance of consciousness immediately after an emergency ventriculoperitoneal shunt and anticoagulation therapy. This case was diagnosed as secondary pseudotumor cerebri (PTC). In order to facilitate the early detection of secondary PTC, it is important to take note of symptoms of intracranial hypertension with no remarkable intracranial lesions and to consider the possibility of PTC, especially in the patients with high risk factors for coagulopathy including lung cancer.

Comparison of costs and outcomes of patients presenting with a rare brainstem syndrome

Devin E. Prior, Vijay Renga

• Pages 21-23
• https://doi.org/10.1016/j.ensci.2018.11.004
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• Abstract

  In this case report we compare two patients presenting with similar symptoms of a brainstem syndrome including ataxia, dysarthria, and diplopia. Their MRIs showed hyperintense FLAIR signal changes with patchy areas of contrast enhancement within the brainstem particularly the pons and cerebellum. The broad differential diagnosis of this brainstem pathology included rhomboencephalitis, neurosarcoidosis, lymphoma, vasculitis, infection, and paraneoplastic or autoimmune process. Patient 1 had an extensive work up including CSF cytology, MRI brain spectroscopy, full body CT, cerebral angiogram, and ultimately brainstem biopsy. None of these studies were diagnostic of a specific etiology and total cost was $176,069. After months of declining medical condition without a clear diagnosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was considered and the patient began steroid therapy resulting in clinical and radiographic improvement. Patient 2 had serum and CSF studies that were negative for infectious, paraneoplastic, and other inflammatory processes. The team diagnosed CLIPPERS and initiated steroid therapy within days resulting in dramatic clinical and radiographic resolution. The workup cost $12,905. Comparison of these cases shows how early awareness of CLIPPERS and a directed diagnostic work up can limit invasive diagnostic testing, expedite initiation of effective therapy, improve patient outcomes, and reduce cost

Paraneoplastic PRES from lymphoma induced hypercalcemia: Case report and review of the literature

Khaled Moussawi, Ethan I. Meltzer, Seth N. Levin, Sashank Prasad

• Pages 24-25
• https://doi.org/10.1016/j.ensci.2018.11.003
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• Abstract

  Hypercalcemia from tumors has been associated with Posterior Reversible Encephalopathy Syndrome (PRES) but the mechanism remains unclear. In this article, we describe a case of PRES caused by hypercalcemia from lymphoma. We summarize the available scientific evidence linking hypercalcemia to failure of cerebral autoregulation and potentially PRES. A major link is the hypomagnesemia induced by hypercalcemia. While this concept requires further clinical testing and validation, it is clinically significant for the management of PRES, even when not directly caused by hypercalcemia

Presence of both anti-contactin 1 and anti-neurofascin 140 antibodies in a case of chronic inflammatory demyelinating polyneuropathy

Hsin-Pin Lin, Kwo Wei David Ho, Miguel Chuquilin

• Pages 38-39
• https://doi.org/10.1016/j.ensci.2018.11.016
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• Abstract

  Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired disorder of peripheral nerves and nerve roots. Its cause is unknown, but recently antibodies to nodal and paranodal proteins have been discovered in a small subset of CIDP patients. These contactin and neurofascin-related immune-mediated neuropathies are thought to be variants of CIDP and often respond suboptimally to standard therapy. Here, we report a patient with both anti-contactin 1 and anti-neurofascin 140 antibodies whose presentation resembled phenotypes of both CIDP variants

Takotsubo syndrome in a stroke patient with carotid artery stenosis

Claudia Stöllberger, Lenka Gerencerova, Josef Finsterer

• Pages 46-48
• https://doi.org/10.1016/j.ensci.2018.11.011
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• Abstract

  Takotsubo syndrome (TTS) is a transient transient left ventricular dysfunction, predominantly affecting elderly women and often preceded by emotional or physical stress. TTS may be the cause as well as the consequence of stroke. We report a 82-years old female with a history of long-standing untreated arterial hypertension who was hospitalized because of a left-sided tongue paralysis and dysarthria. Cerebral magnetic resonance imaging showed ischemic lesions in the territory of the right middle cerebral artery affecting the capsula interna and gyrus praecentralis. The carotid and cerebral arteries showed extensive atherosclerotic wall irregularities, a high-grade stenosis of the M1-segment of the right middle cerebral artery and a 60% stenosis of the internal carotid artery at its origin. Elevated creatine-kinase and Pro-brain-natriuretic peptide levels and development of new ischemic signs in the electrocardiogram suggested myocardial infarction, although the patient did not complain about cardiac symptoms. Echocardiography showed apical ballooning which resolved during the following days. The patient refused coronary angiography why the diagnosis of TTS was not completely established. However, normalization of echocardiogram and ECG were indicative for TTS.

  TTS has to be considered in stroke patients, irrespective of their etiology. Since patients often do not report typical symptoms or may even be asymptomatic, TTS can be overlooked. If the ECG in stroke patients shows signs of myocardial ischemia, troponin and BNP levels should be measured whose ratio may even help to differentiate between TTS and myocardial infarction. Echocardiography, coronary angiography and follow-up investigations are needed to confirm the diagnosis of TTS.

Reversible neurogenic dysphagia: A rare presentation of vitamin B₁₂ deficiency

Justin A. Edward, Amelia Bowman, Daniel B. Heppe

• Pages 31-32
• https://doi.org/10.1016/j.ensci.2018.11.005
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Delayed cortical blindness in hypoxic-ischemic encephalopathy

Sang Won Lee, Haein Bak, Seok-Jin Choi, Yong-Soo Baek

• Pages 33-34
• https://doi.org/10.1016/j.ensci.2018.11.020
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Two cases of late-onset neuromyelitis optica spectrum disorder initially presenting with isolated cerebral white matter lesions

Tai Otani, Takashi Irioka, Yuko K Takahashi, Kazumasa Soga, ... Takanori Yokota

• Pages 35-37
• https://doi.org/10.1016/j.ensci.2018.11.008
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MR T2 high image of longus colli muscle without tendinous calcification; A suggestive sign of cervical spinal infection

Yuji Shiga, Masaru Kuriyama, Keisuke Tachiyama, Yuhei Kanaya, ... Akio Tanaka

• Pages 49-50
• https://doi.org/10.1016/j.ensci.2018.08.002
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Follow-on glatiramer acetate

Jeffrey A. Cohen, Christian Wolf, Krzysztof Selmaj, Roel Arends

• Pages 51-52
• https://doi.org/10.1016/j.ensci.2018.11.019
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Response to the Letter-to-the Editor by Cohen et al. concerning our eNeurologicalSci article, Melamed-Gal, et al. Physicochemical, biological, functional and toxicological characterization of the European follow-on glatiramer acetate product as compared with Copaxone. eNeurologicalSci 2018;12:19–30.https://doi.org/10.1016/j.ensci.2018.05.006

Sigal Melamed-Gal, Pippa Loupe, Bracha Timan, Vera Weinstein, ... Iris Grossman

• Pages 53-55
• https://doi.org/10.1016/j.ensci.2018.11.007
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Evaluating layered stigma from comorbid HIV and epilepsy among Zambian adults

Melissa A. Elafros, Joseph C. Gardiner, Izukanji Sikazwe, Jason F. Okulicz, ... Gretchen L. Birbeck

• Pages 56-62
• https://doi.org/10.1016/j.ensci.2017.12.001
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• Abstract

  Background and purpose

  Stigma hinders care for patients with neurologic illness. Layered stigma due to comorbid disease is common yet poorly characterized due to lack of instruments. Epilepsy and HIV are prototypical stigmatized conditions widespread in sub-Saharan Africa.

  Methods

  We assessed layered stigma among people with HIV and epilepsy (n = 21), epilepsy only (n = 88), and HIV only (n = 40) in Zambia. Epilepsy-associated stigma was assessed using the Stigma Scale of Epilepsy and Jacoby's Stigma Scale. HIV-related stigma was assessed using the HIV/AIDS Stigma Instrument-People Living with HIV/AIDS and Jacoby's Stigma Scale. Stigma was compared across groups using χ² tests.

  Results

  55% (60/109) with epilepsy reported some epilepsy-associated stigma and 20% (12/61) with HIV reported HIV self-stigmatization. Those with HIV and epilepsy were more likely to associate seizures with fear (OR 6.1 [95% CI: 1.3–27.9]) and epilepsy with dependence (OR 4.6 [1.1–19.6]), controlling for age, gender, marital status, and employment. Those with comorbid disease were more likely to report they were "no longer a person" and felt "blamed" for their HIV. Controlling for age and gender, the difference in depersonalization remained (OR: 6.4 [1.1–36.1]).

  Conclusion

  Individuals carrying the burden of one stigmatized condition may be more vulnerable to stigma from a comorbid disease.

Building a network for multicenter, prospective research of central nervous system infections in South America: Process and lessons learned

Christina Nelson, Nicanor Mori, Thanh Ton, Joseph Zunt, ... I. Reyes

• Pages 63-69
• https://doi.org/10.1016/j.ensci.2018.07.001
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• Abstract

  Multicenter collaborative networks are essential for advancing research and improving clinical care for a variety of conditions. Research networks are particularly important for central nervous system infections, which remain difficult to study due to their sporadic occurrence and requirement for collection and testing of cerebrospinal fluid. Establishment of long-term research networks in resource-limited areas also facilitates diagnostic capacity building, surveillance for emerging pathogens, and provision of appropriate treatment where needed. We review our experience developing a research network for encephalitis among twelve hospitals in five Peruvian cities since 2009. We provide practical suggestions to aid other groups interested in advancing research on central nervous system infections in resource-limited areas.