Preparedness of Filipino Neurologists on the Provision of Medical Care Toward Patients of the Lesbian, Gay, Bisexual, Transgender, Queer Plus Community.

The study aimed to describe the preparedness of active members of the Philippine Neurological Association (PNA) in providing medical care to LGBTQ+ patients. We electronically sent out a 21-item self-administered online survey adapted from the 2019 American Academy of Neurology LGBTQ+ Survey Task Force to 511 active members of PNA that included questions about demographic information, knowledge, attitude, and clinical practices. Descriptive statistics were used to analyze variables. Text responses were transcribed and summarized. Seventy-nine (15.5%) of 511 PNA members participated. Most participants were aware of local (53%) and national (56%) barriers that preclude patients in the LGBTQ+ sector from accessing quality health care. The majority (90%) of participants agreed that LGBTQ+ patients experience disproportionate levels of physical and psychological problems. Forty-two percent (42%) of respondents believed that sexual and gender issues have no bearing on neurological management, although a majority (53%) reported individualizing their management considering these issues. The majority were cognizant of the challenges that LGBTQ+ patients face in the health care system. However, awareness has not translated into modifications in neurological management. The openness of the participants to educational opportunities concerning health care related to LGBTQ+ can be leveraged to address this gap.

The practice of teleneurology in the Philippines during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The practice of teleneurology provided an accessible and safe method of consultation during the COVID-19 pandemic. We aimed to describe the practice of teleneurology among Filipino neurologists and determine the factors affecting its adoption using the unified theory of acceptance and use of technology (UTAUT) model and its constructs, namely performance expectancy, effort expectancy, social influence, and facilitating conditions. METHODS: This was a cross-sectional survey conducted online last October 2020 involving adult and pediatric neurologists in the Philippines. The internal consistency of the questionnaire adapted from UTAUT model was determined using Cronbach's alpha. We performed logistic regression analysis to determine which constructs of the UTAUT model were significant factors on the intent to practice teleneurology. RESULTS: The study yielded a 28.8% response rate. Among the respondents (n1 = 147), 95.2% (n2 = 140) practiced teleneurology during the pandemic, and 77.6% (n1 = 147) planned to continue it after the pandemic. Teleneurology was mostly done on an outpatient basis on social media platforms via videoconferencing due to easier access for both end-users. The UTAUT model explained 80.9% (95% CI 0.76, 0.86a) of the total variation. Performance expectancy and facilitating conditions affect the intent to use teleneurology. CONCLUSIONS: Due to the limited resources and knowledge of its practice, infrastructural support and benefit awareness campaigns would be beneficial to increase its adoption, especially in developing countries.

Wernicke-Korsakoff Syndrome in Hyperemesis Gravidarum: A Case Report and Literature Review.

BACKGROUND: Wernicke-Korsakoff syndrome (WKS) is a triad of ophthalmoplegia, ataxia and memory deficits due to thiamine insufficiency resulting from under- or untreated Wernicke's encephalopathy (WE), which may be associated with hyperemesis gravidarum (HEG). CASE PRESENTATION: We present a case of a 36-year-old Filipino woman in her first trimester with HEG, along with the WKS triad and abnormal hyperintense signals in the bilateral thalami and midbrain, left occipital lobe, periaqueductal gray matter and pontine periventricular areas. Neurologic deficits partially improved but persisted despite intravenous thiamine administration. EVIDENCE REVIEW: A review of current treatments for WE, and the prevention and neurocognitive recovery of WKS was done. The beneficial effects of thiamine for acute WKS are supported by several case reports and clinical experience. Evidence from one randomized controlled trial wherein thiamine was given in various doses for treating WE or preventing WKS in an alcohol-dependent population is limited by methodological issues. Rehabilitation and pharmacotherapy for neurocognitive recovery seems promising, but they have inadequate evidentiary support. More robust studies on multi-modal strategies are warranted to facilitate the neurocognitive recovery of patients with WKS.

Re-examining the effects of high-dose intravenous methylprednisolone for secondary progressive multiple sclerosis.

Background/objective: Intravenous methylprednisolone (IVMP) is previously given to secondary progressive multiple sclerosis (SPMS) patients. This study aimed to re-examine the effects of IVMP in SPMS. Materials & methods: Major electronic databases were searched for randomized controlled trials. Results: Four randomized controlled trials were included. IVMP may be inferior to mitoxantrone (MTX) in terms of expanded disability status scale (EDSS) improvement. There was no significant difference in terms of EDSS reduction and magnetic resonance imaging (MRI) plaque reduction when IVMP + MTX were compared with MTX. There is no significant difference between IVMP and cyclophosphamide based on EDSS progression and relapse reduction. Conclusion: IVMP should not be routinely used as treatment for SPMS and is not recommended as an alternative treatment for SPMS.

Lay abstract Secondary progressive multiple sclerosis (SPMS) is a subtype of multiple sclerosis that is associated with degeneration of the nervous system. It is a disabling condition and unlike the relapsing-remitting form of multiple sclerosis, the approved medicines for SPMS are fewer and not readily accessible in developing countries because of cost and availability. Thus, neurologists in these areas have fewer treatment options for SPMS. One of these is intravenous methylprednisolone (IVMP), which is an affordable drug. This study looked at the evidence about IVMP in SPMS. However, the evidences are few and do not support the use of IVMP in SPMS because of a lack of efficacy in reducing disability and abnormal findings in the magnetic resonance imaging.

Consensus recommendation on the use of therapeutic plasma exchange for adult neurological diseases in Southeast Asia from the Southeast Asia therapeutic plasma exchange consortium.

Therapeutic plasma exchange (TPE) is an effective and affordable treatment option in most parts of Southeast Asia (SEA). In 2018, the SEA TPE Consortium (SEATPEC) was established, consisting of regional neurologists working to improve outcome of various autoimmune neurological diseases. We proposed an immunotherapeutic guideline prioritizing TPE for this region. We reviewed disease burden, evidence-based treatment options, and major guidelines for common autoimmune neurological disorders seen in SEA. A modified treatment algorithm based on consensus agreement by key-opinion leaders was proposed. Autoimmune antibody diagnostic testing through collaboration with accredited laboratories was established. Choice of first-line immunotherapies (IVIg/corticosteroid/TPE) is based on available evidence, clinicians' experience, contraindications, local availability, and affordability. TPE could be chosen as first-line therapy for GBS, CIDP, MG (acute/short term), IgG, A paraproteinemic neuropathy, and NMDAR encephalitis. Treatment is stopped for acute monophasic conditions such as GBS and ADEM following satisfactory outcome. For chronic immune disorders, a therapy taper or long-term maintenance therapy is recommended depending on the defined clinical state. TPE as second-line treatment is indicated for IVIg or corticosteroids refractory cases of ADEM, NMOSD (acute), MG, and NMDAR/LGI1/CASPR2/Hashimoto's encephalitis. With better diagnosis, treatment initiation with TPE is a sustainable and effective immunotherapy for autoimmune neurological diseases in SEA.

Efficacy and tolerability of azathioprine for neuromyelitis optica spectrum disorder: A systematic review and meta-analysis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory and autoimmune disorder of the central nervous system that typically presents with optic neuritis and myelitis. Azathioprine (AZA) is one of the available immunotherapies with purported beneficial effects for patients with NMOSD. At present, there are no systematic reviews that extensively pooled the effects of AZA compared to other interventions for this condition. The objective of this study, therefore, is to determine the efficacy and safety of AZA in patients with NMOSD using systematic review of relevant studies. METHODS: Major health electronic databases, which included CENTRAL, MEDLINE, EMBASE, Scopus, LILACS, ClinicalTrials.gov, and HERDIN, were searched from May 2017 to November 2018 for relevant studies involving adult and pediatric patients with NMOSD. Randomized controlled trials, and either prospective or retrospective cohort designs that assessed the reduction or prevention of relapse or disability and the occurrence of adverse events related to AZA use compared to placebo or to other active drugs were considered. Assessment of risk of bias was performed using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. RESULTS: From a total of 273 records, 9 relevant studies (1 randomized controlled trial (RCT), 3 prospective cohort studies, 5 retrospective studies) which involved a total of 977 patients, were included. One RCT and several observational studies revealed that AZA regimen may be inferior to rituximab in terms of annualized relapse rate, reduction of disability as measured by the expanded disability status scale (EDSS), risk for relapse and relapse-free rate. Efficacy data were very limited in the comparison of AZA to mycophenolate mofetil (MMF), to cyclophosphamide, and to interferon-ß for patients with NMOSD. Occurrence of any adverse event, elevated liver enzymes/hepatoxicity, leukopenia and hair loss associated with AZA use were significantly greater compared to MMF, which may lead to medication noncompliance. CONCLUSION: AZA improves relapses and disability in patients with NMOSD but this regimen is associated with relatively frequent adverse events based on limited published evidences. More well-conducted clinical trials are necessary to establish with certainty the beneficial and harmful effects of AZA in patients with NMOSD.

A rare mimic of acute stroke: rapidly progressing Miller-Fisher Syndrome to acute motor and sensory axonal neuropathy variant of Guillain-Barre Syndrome.

Ophthalmoplegia, ataxia and areflexia characterise the clinical triad of Miller-Fisher Syndrome (MFS). When the disease presents acutely, it can mimic posterior circulation stroke. We describe a case of an adult patient presenting with sudden dizziness, diplopia, vomiting, and loss of balance. She was initially managed as a case of a brainstem stroke, but the progression of craniopathies without deterioration in sensorium coupled with areflexia clinched the diagnosis of MFS two days into her admission. On the third day, her MFS progressed rapidly to acute motor and sensory axonal neuropathy (AMSAN) variant of Guillain-Barre Syndrome, a rare occurrence in patients with MFS, with only four reported cases including our own. Among the four cases, ours is the only one still non-ambulatory eight months after the initial onset of symptoms. The case highlights the importance of early recognition of MFS in patients with ophthalmoplegia and ataxia despite initially normal reflexes.

Efficacy and tolerability of mitoxantrone for neuromyelitis optica spectrum disorder: A systematic review.

The review assessed the efficacy and tolerability of mitoxantrone in patients with neuromyelitis optica spectrum disorder (NMOSD). Eight articles were reviewed with a total of 117 patients. Annualized relapse rate and progression of disability dramatically decreased post-treatment in most studies. Mitoxantrone was generally tolerated. Only one patient developed acute myeloid leukemia, which lead to septicemia and death. No serious cardiotoxicity was reported. Mitoxantrone may be effective in reducing the frequency of relapse and slowing down the progression of disability in patients with NMOSD. The risk of cardiotoxicity and leukemia detains it as a second-line agent for NMOSD.

Corrigendum: Validation of a Questionnaire for Distinguishing X-Linked Dystonia Parkinsonism From Its Mimics.

[This corrects the article DOI: 10.3389/fneur.2018.00830.].

Validation of a Questionnaire for Distinguishing X-Linked Dystonia Parkinsonism From Its Mimics.

Objectives: X-linked dystonia parkinsonism (XDP) is a neurodegenerative movement disorder endemic to the island of Panay in the Philippines. We undertook a population-based prevalence study to enumerate all cases of XDP in Panay. We first developed a 4-item questionnaire to distinguish XDP suspects from the general population. In the present study we aimed to revalidate this questionnaire to distinguish XDP from similar conditions so as to give it greater utility in the clinical setting. Patients and Methods: A total of 306 subjects (114 cases and 192 controls) were screened in from the 16 towns and 1 city of Capiz province. Their responses to the previously developed 4-item questionnaire were collected and multivariable logistic regression was performed to develop a predictive model. The accuracy of the model was determined by using it on a subset of patients; then, a scoring system based on the model coefficients was established. Results: With a cut-off score of 6, the questionnaire had an accuracy of 70.7% (95% CI 0.57-0.82), a sensitivity of 84.6 % (95% CI 0.65-0.96) and a specificity of 59.4 % (95% CI 0.41-0.76). The item on "shuffling of feet" was the strongest predictor in distinguishing XDP from its common mimics. Conclusion: We were able to revalidate a simple, four-item questionnaire that could distinguish XDP from its common mimics with fair accuracy. The questionnaire along with other clinical features can be used to determine which patients need specialty evaluation and genetic testing to verify a diagnosis of XDP.

Validation of the XDP-MDSP rating scale for the evaluation of patients with X-linked dystonia-parkinsonism.

X-linked dystonia-parkinsonism(XDP) is a neurodegenerative disorder endemic to the Philippines. A rating scale was developed by the authors under the guidance of the Movement Disorder Society of the Philippines (MDSP) to assess XDP severity and progression, functional impact, and response to treatment in future clinical trials. Our main objective was to validate our new scale, the XDP-MDSP scale. The initial validation process included pragmatic testing to XDP patients followed by a modified Delphi procedure with an international advisory panel of dystonia, parkinsonism and scale development experts. Pearson correlation was used to assess construct validity of our new scale versus the assess construct validity of our new scale versus standard dystonia, parkinsonism, non-motor and functional scales; and also to assess divergent validity against behavioral and cognitive scales. The 37-item XDP-MDSP scale has five parts: I-dystonia, II-parkinsonism, III-non-motor features, IV-ADL, and V-global impression. After initial validation, the scale was administered to 204 XDP patients. Inter-domain correlation for the first four parts was acceptable. The correlation between these domains and the global rating was slightly lower. Correlations between Parts I, II, III, and IV versus standard dystonia, parkinsonism, non-motor and functional scales were acceptable with values ranging from 0.323 to 0.428. For divergent validity, a significant correlation was seen with behavioral scales. No significant correlation was noted with the cognitive scale. The proposed XDP-MDSP scale is internally valid but the global rating subscale may need to be modified or eliminated. While there is convergent validity, divergent validation was successful only on cognitive and not behavioral scales. The frequent co-occurrence of anxiety and depression, and its effect on the motor and functional state, may explain this finding.

New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3).

X-linked recessive dystonia-parkinsonism is a rare movement disorder that is highly prevalent in Panay Island in the Philippines. Earlier studies identified seven different genetic alterations within a 427-kb disease locus on the X chromosome; however, the exact disease-causing variant among these is still not unequivocally determined. To further investigate the genetic cause of this disease, we sequenced all previously reported genetic alterations in 166 patients and 473 Filipino controls. Singly occurring variants in our ethnically matched controls would have allowed us to define these as polymorphisms, but none were found. Instead, we identified five patients carrying none of the disease-associated variants, and one male control carrying all of them. In parallel, we searched for novel single-nucleotide variants using next-generation sequencing. We did not identify any shared variants in coding regions of the X chromosome. However, by validating intergenic variants discovered via genome sequencing, we were able to define the boundaries of the disease-specific haplotype and narrow the disease locus to a 294-kb region that includes four known genes. Using microarray-based analyses, we ruled out the presence of disease-linked copy number variants within the implicated region. Finally, we utilized in silico analysis and detected no strong evidence of regulatory regions surrounding the disease-associated variants. In conclusion, our finding of disease-specific variants occurring in complete linkage disequilibrium raises new insights and intriguing questions about the origin of the disease haplotype, the existence of phenocopies and of reduced penetrance, and the causative genetic alteration in XDP.

Diagnostic features of tuberculous meningitis: a cross-sectional study.

BACKGROUND: Tuberculous meningitis (TBM) is a common central nervous system infection in the Philippines; however it is difficult to diagnose as findings are non-specific. Hence we decided to determine if, among patients with chronic meningitis syndrome, the following are associated with the diagnosis: new-onset seizures; focal neurologic deficit; pulmonary tuberculosis (PTB) on chest X-ray; cerebrospinal fluid (CSF) pleocytosis with lymphocytic predominance; decreased CSF glucose; increased CSF protein. METHODS: Adult patients with suspected TBM were enrolled after informed consent was obtained. Baseline physical examination and diagnostic tests including CT scan of the head with contrast and CSF analysis for acid fast bacilli (AFB) smear, TB culture and cryptococcal antigen detection were done and results collected. Definite TBM was defined as positive AFB smear or positive TB culture or positive basal meningeal enhancement on CT contrast study. Logistic regression was done to determine which were associated with a diagnosis of TBM. RESULTS: 91 patients were included. Using the gold standard criteria mentioned above, 44 had definite TBM; but if subsequent clinical course and response to anti-Koch's therapy are considered, 68 had a final diagnosis of TBM. After logistic regression was performed, only abnormal CSF (the combination of CSF pleocytosis with lymphocytic predominance, decreased CSF glucose, and increased CSF protein) was associated with the diagnosis of TBM. CONCLUSION: In patients with chronic meningitis syndrome, only abnormal CSF was associated with the diagnosis of TBM.

Oral pharmacological treatment of X-linked dystonia parkinsonism: successes and failures.

There is a paucity of published literature on the different oral medications tried for X-linked dystonia parkinsonism (XDP). In practice, most XDP patients are tried or have been tried on medications typically used for patients with generalized dystonia. These drugs include anticholinergic agents, baclofen, clonazepam and other benzodiazepines, tetrabenazine, and clozapine. Although several articles have shown that these classes of drugs are beneficial for patients with generalized dystonia, none have been systematically studied specifically for XDP patients. We are currently conducting the first randomized, placebo-controlled trial on the use of levodopa for the symptomatic treatment of XDP. This article reviews the data on the various dystonia medications that have been used in XDP.

Understanding XDP through imaging, pathology, and genetics.

The X-linked dystonia-parkinsonism (XDP) is a severe, progressive, adult-onset, X-linked endemic disorder in Filipinos, which is characterized by dystonic movements that start in the third or fourth decade, and replaced by parkinsonism beyond the 10th year of illness. Understanding the pathophysiology of XDP and development of rational therapies will depend on observations from imaging, pathological, and genetic studies. In this paper we summarize the results of these studies on patients with XDP. The cranial magnetic resonance imaging shows hyperintense putaminal rim in both dystonic and parkinsonian stages, and atrophy of the caudate head or putamen in the parkinsonian stage. Neuropathological findings show atrophy of the caudate nucleus and putamen, with mild to severe neuronal loss and gliosis. In the neostriatum, the dystonic phase of XDP shows the involvement of striosomes and matrix sparing, while the later, i.e., parkinsonian phase, shows matrix involvement as well. In the dystonic phase, the loss of striosomal inhibitory projections lead to disinhibition of nigral dopaminergic neurons, perhaps resulting in a hyperkinetic state; while in the parkinsonian phase, severe and critical reduction of matrix-based projection may result in extranigral parkinsonism. Genetic sequencing of the XDP critical region in Xq13.1 has revealed an SVA retrotransposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pathology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to more rational and directed therapies.

The unique phenomenology of sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag").

Sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Islands in 1975. XDP manifests predominantly as torsion dystonia, later combined with or sometimes replaced with parkinsonism. Within the Island of Panay, the prevalence rate is highest in the province of Capiz, where 1:4000 men suffer from the disorder. There is a high degree of penetrance and generalization. While women often serve as carriers, XDP is not limited to men. An updated XDP Philippine registry (as of January 2010) has identified 505 cases, with 500 males and 5 females. While some report that females may carry a milder form of the disorder, in our experience, both sexes generally follow a similar progressive clinical course.