Neurology International

16 pages, 606 KiB

Open AccessReview

Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review

by Amber N. Edinoff, Emily D. Ellis, Laura M. Nussdorf, Taylor W. Hill, Elyse M. Cornett, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(1), 294-309; https://doi.org/10.3390/neurolint14010024 - 17 Mar 2022

Cited by 9 | Viewed by 3956

Abstract

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is [...] Read more.

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association. Full article

(This article belongs to the Special Issue Advances in the Treatment of Schizophrenia)

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10 pages, 267 KiB

Open AccessArticle

Neuromyelitis Optica Spectrum Disorder in Central America and the Caribbean: A Multinational Clinical Characterization Study

by Fernando Gracia, Deyanira Ramírez, Alexander Parajeles-Vindas, Alejandro Díaz, Amado Díaz de la Fé, Nicia Eunice Ramírez Sánchez, Romy Castro Escobar, Luis Alberto García Valle, Roberto Weiser, Biany Santos, Awilda Candelario, Aron Benzadon, Pahola Araujo, Carlos Valderrama, Mario Larreategui, Gabriela Carrillo, Karla Gracia, Johana Vázquez-Céspedes, Priscilla Monterrey-Alvarez, Kenneth Carazo-Céspedes, Alfredo Sanabria-Castro, Gustavo Miranda-Loria, Andrea Balmaceda-Meza, Ligia Ibeth Portillo Rivera, Irma Olivera Leal, Luis Cesar Rodriguez Salinas, Arnold Thompson, Ericka López Torres, Daniel Enrique Pereira, Carolina Zepeda, César Abdón López, Ernesto Arturo Cornejo Valse, Karla Zinica Corea Urbina, Marco Antonio Urrutia, Ivonne Van Sijtveld, Blas Armien and Victor M. Rivera Show full author list Hide full author list

Neurol. Int. 2022, 14(1), 284-293; https://doi.org/10.3390/neurolint14010023 - 17 Mar 2022

Cited by 7 | Viewed by 3566

Abstract

Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and [...] Read more.

Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0–52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren’s syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0–3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08–0.41) and 0.73/100,000 (incidence 0.02–0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region. Full article

13 pages, 1785 KiB

Open AccessArticle

Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study

by Jannapas Tharavichitkun, Tinonkorn Yadee, Poomchai Angkaow and Thanarat Suansanae

Neurol. Int. 2022, 14(1), 271-283; https://doi.org/10.3390/neurolint14010022 - 15 Mar 2022

Cited by 3 | Viewed by 3739

Abstract

The brand interchangeability of antiepileptic drugs (AEDs) is a topic of debate, especially regarding their therapeutic equivalence. This study evaluates the efficacy and tolerability of generic levetiracetam compared to the brand-name equivalent in a routine clinical setting. We conducted a retrospective study, examining [...] Read more.

The brand interchangeability of antiepileptic drugs (AEDs) is a topic of debate, especially regarding their therapeutic equivalence. This study evaluates the efficacy and tolerability of generic levetiracetam compared to the brand-name equivalent in a routine clinical setting. We conducted a retrospective study, examining patients with stable seizure frequency who received generic levetiracetam after the brand-name drug. During the six-month substitution period, changes in seizure frequency, hospitalization due to seizure exacerbation, adverse events, composite outcomes related to adjusting the AED dosage, and switching back to original levetiracetam were analyzed. Seventy-five patients were enrolled; the majority (85.3%) had focal onset seizures, and almost half (49.3%) had refractory epilepsy. Six months after the substitution, the mean seizure frequency per month was not significantly different (3.15 ± 14.47 vs. 2.77 ± 11.41; p = 0.970). In patients with controlled seizures before the change, the seizure frequency increased significantly (0.56 ± 1.83 vs. 0.03 ± 0.16; p = 0.012). Adverse events occurred in six patients. We have observed recurrent seizures or adverse events from 14 days after the transition. The original drug return rates due to recurrent seizures and adverse events were 5.3% and 1.3%, respectively. Generic levetiracetam might not show therapeutic equivalence to the original molecule, especially in patients adequately controlled by the brand-name drug. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

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10 pages, 4072 KiB

Open AccessArticle

Brain Magnetic Resonance Imaging Findings in Infantile Spasms

by Osama Y. Muthaffar

Neurol. Int. 2022, 14(1), 261-270; https://doi.org/10.3390/neurolint14010021 - 3 Mar 2022

Cited by 3 | Viewed by 4376

Abstract

Background: Infantile spasms are an age-specific epileptic disorder. They occur in infancy and early childhood. They can be caused by multiple etiologies. Structural abnormalities represent an important cause of infantile spasms. Brain magnetic resonance imaging (MRI) is one of the integral modalities in [...] Read more.

Background: Infantile spasms are an age-specific epileptic disorder. They occur in infancy and early childhood. They can be caused by multiple etiologies. Structural abnormalities represent an important cause of infantile spasms. Brain magnetic resonance imaging (MRI) is one of the integral modalities in the evaluation of this condition. Purpose: The aim of this study is to review and analyze the clinical characteristics and brain MRI findings in a cohort of children diagnosed with infantile spasms. Material and Methods: A cohort of fifty-six children diagnosed with infantile spasms in infancy and early childhood was included. All of them underwent brain MRI for evaluation. The study was conducted in the period from January 2016 to January 2020. Results: Females comprised 57% of the cohort. The mean age for seizure onset was 5.9 months (SD 2.7). Forty-one patients (73%) had active epilepsy, and 51% were diagnosed with global developmental delay. Consanguinity was present in 59% of the cohort. Most of the follow-up MRIs showed structural abnormalities (84%). Hypoxia was reported in 17% of MRIs. Malformations of cortical development were seen in five patients. Brain MRI findings were normal in 16% of patients, and delayed myelination was seen in nineteen patients. Most of the children with active epilepsy (64%) and developmental delay (82%) had an abnormal brain MRI. It was noticed that abnormal second brain MRIs were more likely to be associated with active epilepsy and developmental delay (p = 0.05). Conclusions: Brain MRI is an integral part of infantile spasms’ clinical evaluation. Infantile spasms and abnormal brain MRI can be associated with active epilepsy and global developmental delay. Full article

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5 pages, 169 KiB

Open AccessEditorial

Publisher’s Note: We Changed Page Numbers to Article Numbers for Articles in Neurology International Volume 1–Volume 12, Issue 2

by Neurology International Editorial Office

Neurol. Int. 2022, 14(1), 256-260; https://doi.org/10.3390/neurolint14010020 - 1 Mar 2022

Viewed by 1776

Abstract

Neurology International [...] Full article

11 pages, 261 KiB

Open AccessArticle

Neurological Screening in Elderly Liver Transplantation Candidates: A Single Center Experience

by Federica Avorio, Gianvincenzo Sparacia, Giovanna Russelli, Aurelio Seidita, Giuseppe Mamone, Rossella Alduino, Fabio Tuzzolino, Salvatore Gruttadauria, Roberto Miraglia, Matteo Bulati and Vincenzina Lo Re

Neurol. Int. 2022, 14(1), 245-255; https://doi.org/10.3390/neurolint14010019 - 25 Feb 2022

Cited by 2 | Viewed by 2548

Abstract

Background: Cerebral small vessels disease (cSVD) is an age-related disorder and risk factor for stroke and cognitive/motor impairments. Neurological complications (NCs) are among the causes of adverse outcomes in older liver transplant recipients. This study sought to determine whether cSVD predicts acute NCs [...] Read more.

Background: Cerebral small vessels disease (cSVD) is an age-related disorder and risk factor for stroke and cognitive/motor impairments. Neurological complications (NCs) are among the causes of adverse outcomes in older liver transplant recipients. This study sought to determine whether cSVD predicts acute NCs in over 65-year-old liver transplant patients. Methods: Data were collected, from a retrospective medical chart review, of 22 deceased donor liver transplant recipients aged 65 years or older with a pre-operative brain magnetic resonance imaging (MRI). We used the Fazekas score (0–3) as a quantitative measurement of the vascular lesion load seen in the MRI. We analyzed all post-operative acute NCs occurring during the hospital stay and any other non-NC. Results: cSVD was recognized in all patients. Neurological complications (NCs) occurred in 18.1% of patients with toxic-metabolic encephalopathy the most frequent diagnosis (13.64%). More severe cSVD was associated with seizures (p = 0.0362), longer hospital stay (p 0.0299), and disability (p 0.0134). In our elderly cohort, hepatic encephalopathy (HE) (p 0.0287) and ascites (p 0.0270) were predictors of NCs after liver transplantation. Ascites and/or variceal bleeding and severity of liver disease were associated with adverse post-operative outcomes. The small sample size limited the statistical analysis power. Conclusions: We present the preliminary data of a single-center retrospective study aimed at understanding the cSVD role on NCs and non-NCs after a liver transplantation in elderly patients. This would encourage a more appropriate multicenter prospective study that will definitely confirm if a neurological screening in old age liver transplant candidates is appropriate. Full article

(This article belongs to the Special Issue Fourth Brainstorming Research Assembly for Young Neuroscientists (BraYn))

33 pages, 7394 KiB

Open AccessArticle

Hypomyelinating Leukodystrophy 8 (HLD8)-Associated Mutation of POLR3B Leads to Defective Oligodendroglial Morphological Differentiation Whose Effect Is Reversed by Ibuprofen

by Sui Sawaguchi, Rimi Suzuki, Hiroaki Oizumi, Katsuya Ohbuchi, Kazushige Mizoguchi, Masahiro Yamamoto, Yuki Miyamoto and Junji Yamauchi

Neurol. Int. 2022, 14(1), 212-244; https://doi.org/10.3390/neurolint14010018 - 16 Feb 2022

Cited by 2 | Viewed by 2886

Abstract

POLR3B and POLR3A are the major subunits of RNA polymerase III, which synthesizes non-coding RNAs such as tRNAs and rRNAs. Nucleotide mutations of the RNA polymerase 3 subunit b (polr3b) gene are responsible for hypomyelinating leukodystrophy 8 (HLD8), which is an autosomal recessive [...] Read more.

POLR3B and POLR3A are the major subunits of RNA polymerase III, which synthesizes non-coding RNAs such as tRNAs and rRNAs. Nucleotide mutations of the RNA polymerase 3 subunit b (polr3b) gene are responsible for hypomyelinating leukodystrophy 8 (HLD8), which is an autosomal recessive oligodendroglial cell disease. Despite the important association between POLR3B mutation and HLD8, it remains unclear how mutated POLR3B proteins cause oligodendroglial cell abnormalities. Herein, we show that a severe HLD8-associated nonsense mutation (Arg550-to-Ter (R550X)) primarily localizes POLR3B proteins as protein aggregates into lysosomes in the FBD-102b cell line as an oligodendroglial precursor cell model. Conversely, wild type POLR3B proteins were not localized in lysosomes. Additionally, the expression of proteins with the R550X mutation in cells decreased lysosome-related signaling through the mechanistic target of rapamycin (mTOR). Cells harboring the mutant constructs did not exhibit oligodendroglial cell differentiated phenotypes, which have widespread membranes that extend from their cell body. However, cells harboring the wild type constructs exhibited differentiated phenotypes. Ibuprofen, which is a non-steroidal anti-inflammatory drug (NSAID), improved the defects in their differentiation phenotypes and signaling through mTOR. These results indicate that the HLD8-associated POLR3B proteins with the R550X mutation are localized in lysosomes, decrease mTOR signaling, and inhibit oligodendroglial cell morphological differentiation, and ibuprofen improves these cellular pathological effects. These findings may reveal some of the molecular and cellular pathological mechanisms underlying HLD8 and their amelioration. Full article

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5 pages, 451 KiB

Open AccessCase Report

Clinical and Genetic Analysis of a Patient with CMT4J

by Leema Reddy Peddareddygari and Raji P. Grewal

Neurol. Int. 2022, 14(1), 207-211; https://doi.org/10.3390/neurolint14010017 - 10 Feb 2022

Cited by 2 | Viewed by 2474

Abstract

We report the clinical and genetic analysis of a patient with a rare form of an autosomal recessive genetic neuropathy, Charcot Marie Tooth (CMT) disease type 4J. She presented at age 62 years with signs and symptoms consistent with a mild neuropathy. The [...] Read more.

We report the clinical and genetic analysis of a patient with a rare form of an autosomal recessive genetic neuropathy, Charcot Marie Tooth (CMT) disease type 4J. She presented at age 62 years with signs and symptoms consistent with a mild neuropathy. The onset of symptoms began approximately ten years earlier. Electrophysiological testing confirmed a demyelinating neuropathy and a comprehensive neuropathy screening for common causes of neuropathy was unrevealing. She underwent commercial whole exome sequencing, analyzing more than eighty genes known to cause neuropathy. Two mutations were detected, c.122T > C, p.Ile41Thr and c.2247dupC, p.Ser750GlnX10 in the FIG4 gene. The p.Ile41Thr mutation, which is paternally inherited, is a recurrent mutation reported in a number of unrelated families of European descent. The patient’s father, also of European descent, provides further evidence supporting a founder effect for this mutation. In most patients carrying the p.Ile41Thr mutation, the neuropathy, unlike our patient, is often severe with early onset. The second mutation, c.2247dupC, p.Ser750GlnX10 is maternally inherited and not previously reported. Furthermore, based upon our protein modeling analysis, c.2247dupC is disease producing, representing a novel pathogenic mutation. Our study of this patient expands the clinical and genetic spectrum of patients with CMT 4J. Full article

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8 pages, 1725 KiB

Open AccessArticle

Serum CGRP Changes following Ultrasound-Guided Bilateral Greater-Occipital-Nerve Block

by Abdelrahman Abbas, Ramez Moustafa, Ali Shalash, Mahmoud Haroun, Randa Amin, Sherien Borham, Ahmed Elsadek and Shahinaz Helmy

Neurol. Int. 2022, 14(1), 199-206; https://doi.org/10.3390/neurolint14010016 - 7 Feb 2022

Cited by 4 | Viewed by 2634

Abstract

Background: Calcitonin-gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal nerve cells, and treatments targeting CGRP are effective in migraines. For headaches that do not respond to pharmacological treatment, minimally invasive techniques such as greater-occipital-nerve block (GONB) can help relieve the pain [...] Read more.

Background: Calcitonin-gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal nerve cells, and treatments targeting CGRP are effective in migraines. For headaches that do not respond to pharmacological treatment, minimally invasive techniques such as greater-occipital-nerve block (GONB) can help relieve the pain and reduce the frequency of headaches. Our study assessed the efficacy of ultrasound-guided greater-occipital-nerve block (USgGONB) in chronic migraines (CM) and its relationship to serum CGRP levels. Methods: Forty chronic migraineurs who underwent bilateral USgGONB using 40 mg triamcinolone and 1 mL lidocaine were recruited and interictal serum CGRP samples were collected immediately before and one month after GONB. The clinical response was evaluated using headache diaries before and one month after USgGONB. The patient response was determined after USgGONB according to the reduction in headache days as a good responder (>50% reduction), poor responder (<50%) or non-responder. Results: Monthly headache days after GONB showed a significant reduction (median, 10 days; range, 8–14.7) compared to before the block (median, 18 days; range, 17–22; p < 0.001). Across all patients, interictal serum CGRP levels after USgGONB were significantly lower than before the block (median, 40 pg/mL (range, 25–60) vs. 145 pg/mL (range, 60–380) (p = 0.001). The pre-treatment interictal CGRP levels showed a significant difference (p = 0.003), as their levels in non-responders (median, 310 pg/mL; interquartile range, 262–350) were significantly higher than those seen in responders, whether poor responders (median, 135 pg/mL; interquartile range, 100–200 pg/mL) or good responders (median, 140 pg/mL; interquartile range, 80–150 pg/mL). Conclusion: the study showed the beneficial effect of USgGONB in chronic migraines that was associated with lowering interictal CGRP levels, implying a potential role for CGRP in the mechanism of action of GONB in CM, and the interictal CGRP level may be used as a predictor for the response to GONB. Full article

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13 pages, 651 KiB

Open AccessReview

Oxytocin, a Novel Treatment for Methamphetamine Use Disorder

by Amber N. Edinoff, Elliot Thompson, Chandler E. Merriman, Mark R. Alvarez, E. Saunders Alpaugh, Elyse M. Cornett, Kevin S. Murnane, Rachel L. Kozinn, Mila Shah-Bruce, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(1), 186-198; https://doi.org/10.3390/neurolint14010015 - 30 Jan 2022

Cited by 11 | Viewed by 8832

Abstract

The treatment of substance abuse with oxytocin is a novel approach to a challenging public health issue that continues to contribute to a growing economic cost for societies worldwide. Methamphetamine addiction is one of the leading causes of mortality worldwide, and despite advances [...] Read more.

The treatment of substance abuse with oxytocin is a novel approach to a challenging public health issue that continues to contribute to a growing economic cost for societies worldwide. Methamphetamine addiction is one of the leading causes of mortality worldwide, and despite advances in understanding the neurobiology of methamphetamine addiction, treatment options are limited. There are no medications that the Food and Drug Administration currently approves for stimulant use disorder. Off-label use of therapies for stimulant misuse include antidepressants, anxiolytics, and milder stimulants as replacement agents. Due to the shortcomings of these attempts to treat a complicated psychiatric disorder, recent attention to oxytocin therapy (OT) has gained momentum in clinical studies as a possible therapy in the context of social stress, social anxiety, social cognition, and psychosis. Oxytocin produces enhanced connectivity between cortical regions. The results from studies in rodents with OT suggest that central neuromodulation of oxytocin may be beneficial across transition states of stimulant dependence and may alleviate intense withdrawal symptoms. Studies of oxytocin in the context of other drugs of abuse, including cocaine, cannabis, and alcohol, also support the potential of oxytocin to treat stimulant use disorder, methamphetamine type. Methamphetamine abuse continues to be a significant cause of distress and dysfunction throughout the world. The effects of oxytocin on methamphetamine use outlined in this review should act as a catalyst for further investigation into the efficacy of treating stimulant use disorder, methamphetamine type with oxytocin in humans. More human-based research should initiate studies involving the long-term efficacy, side effects, and patient selection. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

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10 pages, 6231 KiB

Open AccessCase Report

Neuroimaging and CSF Findings in Patients with Autoimmune Encephalitis: A Report of Eight Cases in a Single Academic Center

by Hongyan Wu, Hongxuyang Yu, Joe Joseph, Shruti Jaiswal, Shreya R. Pasham and Shitiz Sriwastava

Neurol. Int. 2022, 14(1), 176-185; https://doi.org/10.3390/neurolint14010014 - 28 Jan 2022

Cited by 4 | Viewed by 4617

Abstract

Autoimmune Encephalitis (AIE) is a rare and complex group of disorders wherein the body’s immune system attacks and causes inflammatory changes in the central nervous system (CNS). It presents with altered mental status and a diverse range of typical and atypical symptoms and [...] Read more.

Autoimmune Encephalitis (AIE) is a rare and complex group of disorders wherein the body’s immune system attacks and causes inflammatory changes in the central nervous system (CNS). It presents with altered mental status and a diverse range of typical and atypical symptoms and neuroimaging and cerebrospinal fluid (CSF) findings. The objective of this article is to highlight the importance of early identification of neurological symptoms, prompt diagnosis with neuroimaging and CSF findings, and timely management for early and complete resolution of the disease and long-term benefits. We report eight AIE cases from a single academic center confirmed by the presence of specific serum and CSF autoantibodies. The patients were mostly women, with imaging findings showing T2-weighted (T2), fluid-attenuated inversion recovery (FLAIR), hyperintensities/changes in cortical/mesio-temporal regions on a magnetic resonance imaging (MRI), and delta brush wave patterns or epileptogenic patterns on an electroencephalogram (EEG). Among the antibodies, the N-methyl-D-aspartate receptor (NMDA-R) antibody (AB) was most frequently identified, and CSF lymphocytosis and elevated CSF glucose were found in majority of the cases, CSF pleocytosis and elevated protein only in a minority of patients, and oligoclonal bands (OCBs) only in NMDA-R encephalitis. Early treatment with intravenous immune globulin (IVIG), steroids, plasmapheresis (PLEX), and rituximab was started in most cases, and all of them responded well and survived, but some had residual symptoms or relapses. Full article

(This article belongs to the Special Issue Advances in Multiple Sclerosis)

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2 pages, 235 KiB

Open AccessEditorial

Acknowledgment to Reviewers of Neurology International in 2021

by Neurology International Editorial Office

Neurol. Int. 2022, 14(1), 174-175; https://doi.org/10.3390/neurolint14010013 - 25 Jan 2022

Viewed by 1706

Abstract

Rigorous peer-reviews are the basis of high-quality academic publishing [...] Full article

10 pages, 2112 KiB

Open AccessCommunication

Extending Thrombolysis in Acute Ischemic Stroke to Primary Care: Early Experiences with a Network-Based Teleneurology Approach

by Francesco Corea, Monica Acciarresi, Laura Bernetti, Pierluigi Brustenghi, Arianna Guidubaldi, Mariangela Maiotti, Sara Micheli, Vilma Pierini, Alessio Gamboni, Giuseppe Calabrò, Chiara Busti, Cesare Magistrato, Gianluca Proietti-Silvestri, Massimo Bracaccia, Valeria Caso and Mauro Zampolini

Neurol. Int. 2022, 14(1), 164-173; https://doi.org/10.3390/neurolint14010012 - 21 Jan 2022

Cited by 2 | Viewed by 3571

Abstract

Background and Purpose—Systemic thrombolysis represents the main proven therapy for acute ischemic stroke, but safe treatment is reported only in well-established stroke units. To extend the use of tissue plasminogen activator (tPA) treatment in primary care hospitals on isolated areas through telemedic was [...] Read more.

Background and Purpose—Systemic thrombolysis represents the main proven therapy for acute ischemic stroke, but safe treatment is reported only in well-established stroke units. To extend the use of tissue plasminogen activator (tPA) treatment in primary care hospitals on isolated areas through telemedic was the purpose of specific initiatives in southern Umbria, Italy. Methods—The stroke center of Foligno established a telestroke network to provide consultations for three local hospitals in southern Umbria. The telemedic system consists of a digital network that includes a two-way video conference system and imaging sharing. The main network hospital established specialized stroke wards/teams in which qualified teams treat acute stroke patients. Physicians in these hospitals are able to contact the stroke centers 24 h per day. Quality data are available to support the safe implementation of the stroke procedures. Those available from governmental authorities and local datasets are volume of hospitalization, in-hospital mortality, 30-days mortality, and discharge setting. Objective of the study was to assess the annual hospitalization volume in both the hub and spoke hospitals for ischemic stroke and appraise the performance of the network after the introduction of the telestroke system. Results—A total of 225 systemic thrombolyses were performed in time period indicated above all hospitals. In the main spoke hospital, 41 procedures were performed after teleconsultations were made available. The thrombolysis rate in the hub hospital ranged between 10% in 2016 and 20% in 2019, while in the spoke hospital was below 5% in 2016 and raised to 15% in 2019. The statistically significant difference, in the number of procedures, between hub and spoke in the beginning of the observation time disappeared after introduction of the telestroke network. No increase of the mortality was found. Conclusions—The present data suggest that systemic thrombolysis indicated via stroke experts in the setting of teleconsultation shows similar complication rates to those reported in the National Institute of Neurological Disorders and Stroke trial. Therefore, tPA treatment is also safe in this context and can be extended to primary hospitals. Full article

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6 pages, 1236 KiB

Open AccessCase Report

Headache Attributed to Temporomandibular Disorder and Primary Cough Headache

by Keita Takizawa, Kentaro Urata, Rena Tanaka, Kana Ozasa, Andrew Young and Noboru Noma

Neurol. Int. 2022, 14(1), 158-163; https://doi.org/10.3390/neurolint14010011 - 17 Jan 2022

Cited by 1 | Viewed by 3713

Abstract

Orofacial pain is a frequent chief complaint of many systemic disorders. A primary cough headache may mimic the clinical symptoms of a temporomandibular disorder (TMD) or may be associated with TMDs. Case report: A 52-year-old man presented with a 1-year history of TMD [...] Read more.

Orofacial pain is a frequent chief complaint of many systemic disorders. A primary cough headache may mimic the clinical symptoms of a temporomandibular disorder (TMD) or may be associated with TMDs. Case report: A 52-year-old man presented with a 1-year history of TMD symptoms with clicking. He presented with the chief complaint of a sudden and severe headache when coughing, sneezing, or crouching. Comprehensive intra- and extra-oral examinations were performed, which revealed myofascial pain involving the right masseter and temporalis muscles, disc displacement with reduction in the right temporomandibular joint, and headache attributed to TMD, but no severe headaches appeared in the cough-induced test at the first visit. Initially, we advised the patient to minimize activities that require jaw function (e.g., chewing), avoid jaw parafunction (e.g., bruxism), and to perform at-home jaw exercises to stretch the jaw muscles. The patient’s symptoms reduced by more than half after the TMD home care and physiotherapy. He was then treated with 75 mg of indomethacin per day, which eliminated his headache. The patient was then referred to a headache specialist, who diagnosed primary cough headache. Full article

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49 pages, 454 KiB

Open AccessConference Report

Abstracts of the Fourth Brainstorming Research Assembly for Young Neuroscientists (BraYn), Italy, 20–22 October 2021

by Giovanni Ferrara

Neurol. Int. 2022, 14(1), 109-157; https://doi.org/10.3390/neurolint14010010 - 14 Jan 2022

Cited by 2 | Viewed by 4796

Abstract

On behalf of the BraYn Association, we are pleased to present the Abstracts of the Fourth Brainstorming Research Assembly for Young Neuroscientists, which was held from 20–22 October 2021. We congratulate all the presenters on their research work and contribution. Full article

(This article belongs to the Special Issue Fourth Brainstorming Research Assembly for Young Neuroscientists (BraYn))

10 pages, 644 KiB

Open AccessSystematic Review

Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review

by Gaurav Nepal, Mahika Khurana, Domenica Herrera Bucheli, Siddhartha Bhandari, Utsav Joshi, Riwaj Bhagat, Jessica Holly Rehrig, Prasun Pudasainee, Yow Ka Shing, Juan Fernando Ortiz, Rajeev Ojha, Bikram Prasad Gajurel, Jonathan Quinonez, Samir Ruxmohan, Trevine Albert, Steven Licata and Joel Stien

Neurol. Int. 2022, 14(1), 99-108; https://doi.org/10.3390/neurolint14010009 - 11 Jan 2022

Cited by 4 | Viewed by 4458

Abstract

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1–2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy [...] Read more.

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1–2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL. Full article

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9 pages, 250 KiB

Open AccessEditor’s ChoiceArticle

Financial Incapacity of Patients with Mild Alzheimer’s Disease: What Neurologists Need to Know about Where the Impairment Lies

by Vaitsa Giannouli and Magda Tsolaki

Neurol. Int. 2022, 14(1), 90-98; https://doi.org/10.3390/neurolint14010008 - 11 Jan 2022

Cited by 11 | Viewed by 3137

Abstract

Research in the last decade has focused on assessing financial capacity and incapacity mainly in old age, but new research has turned to address the question of how financial incapacity can be predicted by cognitive factors. The aim of this study was to [...] Read more.

Research in the last decade has focused on assessing financial capacity and incapacity mainly in old age, but new research has turned to address the question of how financial incapacity can be predicted by cognitive factors. The aim of this study was to identify which cognitive domains predict financial capacity and the relevant cognitive skills of patients with mild Alzheimer’s disease (AD) in order to assist neurologists in functional assessment and further patient referral. In this study, 109 patients diagnosed with mild AD were examined with a number of neuropsychological tests: Mini-Mental State Examination (MMSE), Functional Rating Scale for Symptoms of Dementia (FRSSD), Functional Cognitive Assessment Scale (FUCAS), Trail Making Test (TMT)-Part B, Rey-Osterrieth Complex Figure Test (ROCFT)-copy condition and delayed recall condition, Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test, Rivermead Behavioural Memory Test (RBMT), digit span forward and backward, WAIS-R digit symbol substitution test, Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). LCPLTAS total score and relevant subdomains were best predicted only by the score of one item coming from MMSE: subtraction of serial sevens. This is the only measure of arithmetic testing in use for the Greek geriatric population. Financial capacity is severely impaired in the group of mild AD patients. In order to prevent financial exploitation cases, neurologists, neuropsychologists, psychiatrists, and geriatrists should pay close attention to the information from the relevant arithmetic question of MMSE, as it is one of the most widely administered screening tests in clinical settings. Full article

(This article belongs to the Collection Brain Health Initiative: Advocacy in Global Neurology)

1 pages, 169 KiB

Open AccessEditorial

COVID-19 Is Changing Our Understanding of the Neuroscience of Viral Infections: What We Can Do to Prepare for the Future?

by Kore Kai Liow and Jason Viereck

Neurol. Int. 2022, 14(1), 89; https://doi.org/10.3390/neurolint14010007 - 6 Jan 2022

Viewed by 2117

Abstract

In the approximately two years since the emergence of COVID-19 (Coronavirus Disease 2019) myriad neurological symptoms have been reported that are seemingly unrelated to each other [...] Full article

(This article belongs to the Special Issue Neurological Aspects of COVID-19: What We Knew Then, What We Know Now, & What We Need to Prepare for in the Future)

14 pages, 308 KiB

Open AccessReview

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

by Amber N. Edinoff, Nicole M. Sanders, Kyle B. Lewis, Tucker L. Apgar, Elyse M. Cornett, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(1), 75-88; https://doi.org/10.3390/neurolint14010006 - 4 Jan 2022

Cited by 14 | Viewed by 6046

Abstract

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss [...] Read more.

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

13 pages, 305 KiB

Open AccessReview

Antipsychotic Use in Pregnancy: Patient Mental Health Challenges, Teratogenicity, Pregnancy Complications, and Postnatal Risks

by Amber N. Edinoff, Niroshan Sathivadivel, Shawn E. McNeil, Austin I. Ly, Jaeyeon Kweon, Neil Kelkar, Elyse M. Cornett, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(1), 62-74; https://doi.org/10.3390/neurolint14010005 - 3 Jan 2022

Cited by 16 | Viewed by 11963

Abstract

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have [...] Read more.

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs. Full article

(This article belongs to the Special Issue Advances in the Treatment of Schizophrenia)

13 pages, 290 KiB

Open AccessReview

Naltrexone Implant for Opioid Use Disorder

by Amber N. Edinoff, Catherine A. Nix, Claudia V. Orellana, Samantha M. StPierre, Erin A. Crane, Blaine T. Bulloch, Elyse M. Cornett, Rachel L. Kozinn, Adam M. Kaye, Kevin S. Murnane and Alan D. Kaye

Neurol. Int. 2022, 14(1), 49-61; https://doi.org/10.3390/neurolint14010004 - 30 Dec 2021

Cited by 16 | Viewed by 5025

Abstract

The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began [...] Read more.

The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began with the introduction of methadone in the 1960s. The approval of oral naltrexone initially showed much promise, as the drug was observed to be highly potent in antagonizing the effects of opioids while producing no opioid agonist effects of its own and having a favorable side effect profile. Patients that routinely take their naltrexone reported fewer days of heroin use and had more negative drug tests than those without treatment. Poor outcomes in OUD patients treated with naltrexone have been directly tied to short treatment time. Studies have shown that naltrexone given orally vs. as an implant at the 6-month interval showed a higher non-compliance rate among those who used oral medications at the 6-month mark and a slower return to use rate. There were concerns that naltrexone could possibly worsen negative symptoms seen in opiate use disorder related to blockade of endogenous opioids that are important for pleasurable stimuli. Studies have shown that naltrexone demonstrated no increase in levels of anxiety, depression and anhedonia in participants and another study found that those treated with naltrexone had a significant reduction in mental health-related hospitalizations. The latter study also concluded that there was no increased risk for mental health-related incidents in patients taking naltrexone via a long-acting implant. Although not yet FDA approved in the United States, naltrexone implant has shown promising results in Europe and Australia and may provide a novel treatment option for opioid addiction. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

15 pages, 319 KiB

Open AccessReview

Guillain-Barré Syndrome in the COVID-19 Pandemic

by Abdullah Ahmad Tawakul, Amal Waleed Al-Doboke, Shahad Ali Altayyar, Seham Abdulhafith Alsulami, Ahlam Musallam Alfahmi and Raghad Turki Nooh

Neurol. Int. 2022, 14(1), 34-48; https://doi.org/10.3390/neurolint14010003 - 24 Dec 2021

Cited by 9 | Viewed by 3789

Abstract

There have been several reported cases of severe acute respiratory syndrome (SARS-CoV-2) infection that were associated with an increased incidence of neurological manifestations, including Guillain–Barré syndrome (GBS). This review aims to present information on the reports of GBS associated with coronavirus disease 2019 [...] Read more.

There have been several reported cases of severe acute respiratory syndrome (SARS-CoV-2) infection that were associated with an increased incidence of neurological manifestations, including Guillain–Barré syndrome (GBS). This review aims to present information on the reports of GBS associated with coronavirus disease 2019 (COVID-19) infection. Our review is retrospective work examining articles published from the 1 April 2020 to the 8 May 2021 in the English language. We used the diagnostic criteria and classification published by the National Institute of Neurological Disorders and Stroke and Brighton Collaboration. GBS is usually a postinfectious syndrome, but GBS in the COVID-19 pandemic also takes on a para-infectious profile. In the reports, the genetic factor has a role in developing GBS in some patients. In conclusion, the association between COVID-19 and GBS is not very clear. Still, one mechanism is strongly associated with COVID-19 and immune-mediated neurological complications, which is molecular mimicry between SARS-CoV-2 and human autoantigens. Full article

23 pages, 47845 KiB

Open AccessArticle

Hypomyelinating Leukodystrophy 7 (HLD7)-Associated Mutation of POLR3A Is Related to Defective Oligodendroglial Cell Differentiation, Which Is Ameliorated by Ibuprofen

by Sui Sawaguchi, Kenji Tago, Hiroaki Oizumi, Katsuya Ohbuchi, Masahiro Yamamoto, Kazushige Mizoguchi, Yuki Miyamoto and Junji Yamauchi

Neurol. Int. 2022, 14(1), 11-33; https://doi.org/10.3390/neurolint14010002 - 22 Dec 2021

Cited by 12 | Viewed by 3116

Abstract

Hypomyelinating leukodystrophy 7 (HLD7) is an autosomal recessive oligodendroglial cell-related myelin disease, which is associated with some nucleotide mutations of the RNA polymerase 3 subunit a (polr3a) gene. POLR3A is composed of the catalytic core of RNA polymerase III synthesizing non-coding RNAs, such [...] Read more.

Hypomyelinating leukodystrophy 7 (HLD7) is an autosomal recessive oligodendroglial cell-related myelin disease, which is associated with some nucleotide mutations of the RNA polymerase 3 subunit a (polr3a) gene. POLR3A is composed of the catalytic core of RNA polymerase III synthesizing non-coding RNAs, such as rRNA and tRNA. Here, we show that an HLD7-associated nonsense mutation of Arg140-to-Ter (R140X) primarily localizes POLR3A proteins as protein aggregates into lysosomes in mouse oligodendroglial FBD−102b cells, whereas the wild type proteins are not localized in lysosomes. Expression of the R140X mutant proteins, but not the wild type proteins, in cells decreased signaling through the mechanistic target of rapamycin (mTOR), controlling signal transduction around lysosomes. While cells harboring the wild type constructs exhibited phenotypes with widespread membranes with myelin marker protein expression following the induction of differentiation, cells harboring the R140X mutant constructs did not exhibit them. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), which is also known as an mTOR signaling activator, ameliorated defects in differentiation with myelin marker protein expression and the related signaling in cells harboring the R140X mutant constructs. Collectively, HLD7-associated POLR3A mutant proteins are localized in lysosomes where they decrease mTOR signaling, inhibiting cell morphological differentiation. Importantly, ibuprofen reverses undifferentiated phenotypes. These findings may reveal some of the pathological mechanisms underlying HLD7 and their amelioration at the molecular and cellular levels. Full article

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10 pages, 454 KiB

Open AccessArticle

Co-Designing a New Yoga-Based Mindfulness Intervention for Survivors of Stroke: A Formative Evaluation

by Tharshanah Thayabaranathan, Maarten A. Immink, Susan Hillier, Rene Stolwyk, Nadine E. Andrew, Philip Stevens, Monique F. Kilkenny, Emma Gee, Leeanne Carey, Amy Brodtmann, Julie Bernhardt, Amanda G. Thrift and Dominique A. Cadilhac

Neurol. Int. 2022, 14(1), 1-10; https://doi.org/10.3390/neurolint14010001 - 21 Dec 2021

Cited by 6 | Viewed by 3819

Abstract

Movement-based mindfulness interventions (MBI) are complex, multi-component interventions for which the design process is rarely reported. For people with stroke, emerging evidence suggests benefits, but mainstream programs are generally unsuitable. We aimed to describe the processes involved and to conduct a formative evaluation [...] Read more.

Movement-based mindfulness interventions (MBI) are complex, multi-component interventions for which the design process is rarely reported. For people with stroke, emerging evidence suggests benefits, but mainstream programs are generally unsuitable. We aimed to describe the processes involved and to conduct a formative evaluation of the development of a novel yoga-based MBI designed for survivors of stroke. We used the Medical Research Council complex interventions framework and principles of co-design. We purposefully approached health professionals and consumers to establish an advisory committee for developing the intervention. Members collaborated and iteratively reviewed the design and content of the program, formatted into a training manual. Four external yoga teachers independently reviewed the program. Formative evaluation included review of multiple data sources and documentation (e.g., formal meeting minutes, focus group discussions, researcher observations). The data were synthesized using inductive thematic analysis. Three broad themes emerged: (a) MBI content and terminology; (b) manual design and readability; and (c) barriers and enablers to deliver the intervention. Various perspectives and feedback on essential components guided finalizing the program. The design phase of a novel yoga-based MBI was strengthened by interdisciplinary, consumer contributions and peer review. The 12-week intervention is ready for testing among survivors of stroke. Full article

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Neurol. Int., Volume 14, Issue 1 (March 2022) – 24 articles

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