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1.
J Neurol ; 271(2): 852-863, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37839041

ABSTRACT

OBJECTIVE: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia. METHODS: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year. RESULTS: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). Higher GAD scores at baseline predicted lower HR-QoL related to general health, pain and emotional well-being, whereas higher SAD scores predicted higher pain-related QoL after 2 years (all p ≤ 0.006). Dystonia severity at baseline predicted social functioning (p = 0.002). Neither dystonic tremor, age, or sex predicted HR-QoL at 2 years. Two latent categories were revealed across the three-time points: Category 1 with higher total HR-QoL scores (mean HR-QoL = 74.4% ± 16.1), susceptible to symptoms of depression and SAD, and Category 2 with lower total HR-QoL scores (mean HR-QoL = 45.5% ± 17.6), susceptible to symptoms of GAD. HR-QoL improved over the course of 1 year irrespective of the use of BoNT. CONCLUSION: The longitudinal impact of psychiatric symptoms on HR-QoL emphasizes the importance of incorporating mental health treatment, in particular also the therapy of anxiety disorders, into treatment regimens for dystonia.


Subject(s)
Dystonia , Dystonic Disorders , Humans , Child, Preschool , Quality of Life/psychology , Tremor/diagnosis , Dystonic Disorders/drug therapy , Pain
2.
Parkinsonism Relat Disord ; 114: 105764, 2023 09.
Article in English | MEDLINE | ID: mdl-37517108

ABSTRACT

BACKGROUND: There are no evidence-based guidelines for data cleaning of electronic health record (EHR) databases in Parkinson's disease (PD). Previous filtering criteria have primarily used the 9th International Statistical Classification of Diseases and Related Health Problems (ICD) with variable accuracy for true PD cases. Prior studies have not excluded atypical or drug-induced parkinsonism, and little is known about differences in accuracy by race. OBJECTIVE: To determine if excluding parkinsonism diagnoses improves accuracy of ICD-9 and -10 PD diagnosis codes. METHODS: We included ≥2 instances of an ICD-9 and/or -10 code for PD. We removed any records with at least one code indicating atypical or drug-induced parkinsonism first in all races, and then in Non-Hispanic White and Black patients. We manually reviewed 100 randomly selected charts per group before and after filtering, and performed a test of proportion (null hypothesis 0.5) for confirmed PD. RESULTS: 5633 records had ≥2 instances of a PD code. 2833 remained after filtering. The rate of true PD cases was low before and after filtering to remove parkinsonism codes (0.55 vs. 0.51, p = 0.84). Accuracy was lowest in Black patients before filtering (0.48, p = 0.69), but filtering had a greater (though modest) impact on accuracy (0.68, p < 0.001). CONCLUSIONS: There was inadequate accuracy of PD diagnosis codes in the largest study of ICD-9 and -10 codes. Accuracy was lowest in Black patients but improved the most with removing other parkinsonism codes. This highlights the limitations of using current real-world EHR data in PD research and need for further study.


Subject(s)
Parkinson Disease , Parkinsonian Disorders , Humans , Electronic Health Records , Parkinson Disease/diagnosis , Parkinson Disease/epidemiology , International Classification of Diseases , Databases, Factual
3.
Handb Clin Neurol ; 193: 187-209, 2023.
Article in English | MEDLINE | ID: mdl-36803811

ABSTRACT

Clinical trials of putative disease-modifying therapies in neurodegeneration have obeyed the century-old principle of convergence, or lumping, whereby any feature of a clinicopathologic disease entity is considered relevant to most of those affected. While this convergent approach has resulted in important successes in trials of symptomatic therapies, largely aimed at correcting common neurotransmitter deficiencies (e.g., cholinergic deficiency in Alzheimer's disease or dopaminergic deficiency in Parkinson's disease), it has been consistently futile in trials of neuroprotective or disease-modifying interventions. As individuals affected by the same neurodegenerative disorder do not share the same biological drivers, splitting such disease into small molecular/biological subtypes, to match people to therapies most likely to benefit them, is vital in the pursuit of disease modification. We here discuss three paths toward the splitting needed for future successes in precision medicine: (1) encourage the development of aging cohorts agnostic to phenotype in order to enact a biology-to-phenotype direction of biomarker development and validate divergence biomarkers (present in some, absent in most); (2) demand bioassay-based recruitment of subjects into disease-modifying trials of putative neuroprotective interventions in order to match the right therapies to the right recipients; and (3) evaluate promising epidemiologic leads of presumed pathogenetic potential using Mendelian randomization studies before designing the corresponding clinical trials. The reconfiguration of disease-modifying efforts for patients with neurodegenerative disorders will require a paradigm shift from lumping to splitting and from proteinopathy to proteinopenia.


Subject(s)
Alzheimer Disease , Parkinson Disease , Humans , Parkinson Disease/genetics , Alzheimer Disease/therapy , Biomarkers , Aging
4.
Mov Disord ; 38(3): 496-501, 2023 03.
Article in English | MEDLINE | ID: mdl-36707401

ABSTRACT

BACKGROUND: Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies. OBJECTIVE: We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies. METHODS: Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration. RESULTS: Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05). CONCLUSIONS: Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Hypokinesia , Parkinson Disease , Synucleinopathies , Tauopathies , Video Recording , Humans , Hypokinesia/complications , Hypokinesia/physiopathology , Logistic Models , Parkinson Disease/complications , Parkinson Disease/pathology , Parkinson Disease/physiopathology , Retrospective Studies , Statistics, Nonparametric , Supranuclear Palsy, Progressive/complications , Supranuclear Palsy, Progressive/pathology , Supranuclear Palsy, Progressive/physiopathology , Synucleinopathies/complications , Synucleinopathies/pathology , Synucleinopathies/physiopathology , Tauopathies/complications , Tauopathies/pathology , Tauopathies/physiopathology , Autopsy , Male , Female , Middle Aged , Aged
5.
Parkinsonism Relat Disord ; 99: 62-64, 2022 06.
Article in English | MEDLINE | ID: mdl-35605513

ABSTRACT

We evaluate the effect of droxidopa on gait and balance measures in nine patients with Parkinson's disease and neurogenic orthostatic hypotension. Computerized gait/balance analysis showed a significant effect of droxidopa in reducing postural sway. Future studies may determine if such effect translates into improvement in postural reflexes and falls.


Subject(s)
Droxidopa , Hypotension, Orthostatic , Parkinson Disease , Antiparkinson Agents/therapeutic use , Droxidopa/therapeutic use , Humans , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/etiology , Parkinson Disease/complications , Parkinson Disease/drug therapy , Reflex
6.
Front Neurol ; 13: 821189, 2022.
Article in English | MEDLINE | ID: mdl-35401394

ABSTRACT

Long-read sequencing (LRS) technologies have been recently introduced to overcome intrinsic limitations of widely-used next-generation sequencing (NGS) technologies, namely the sequencing limited to short-read fragments (150-300 base pairs). Since its introduction, LRS has permitted many successes in unraveling hidden mutational mechanisms. One area in clinical neurology in need of rethinking as it applies to genetic mechanisms is essential tremor (ET). This disorder, among the most common in neurology, is a syndrome often exhibiting an autosomal dominant pattern of inheritance whose large phenotypic spectrum suggest a multitude of genetic etiologies. Exome sequencing has revealed the genetic etiology only in rare ET families (FUS, SORT1, SCN4A, NOS3, KCNS2, HAPLN4/BRAL2, and USP46). We hypothesize that a reason for this shortcoming may be non-classical genetic mechanism(s) underpinning ET, among them trinucleotide, tetranucleotide, or pentanucleotide repeat disorders. In support of this hypothesis, trinucleotide (e.g., GGC repeats in NOTCH2NLC) and pentanucleotide repeat disorders (e.g., ATTTC repeats in STARD7) have been revealed as pathogenic in patients with a past history of what has come to be referred to as "ET plus," bilateral hand tremor associated with epilepsy and/or leukoencephalopathy. A systematic review of LRS in neurodegenerative disorders showed that 10 of the 22 (45%) genetic etiologies ascertained by LRS include tremor in their phenotypic spectrum, suggesting that future clinical applications of LRS for tremor disorders may uncover genetic subtypes of familial ET that have eluded NGS, particularly those with associated leukoencephalopathy or family history of epilepsy. LRS provides a pathway for potentially uncovering novel genes and genetic mechanisms, helping narrow the large proportion of "idiopathic" ET.

7.
J Neurol ; 269(7): 3511-3521, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35024921

ABSTRACT

BACKGROUND: Movement disorders can be associated with anti-neuronal antibodies. METHODS: We conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospinal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variable selection and recursive partitioning and regression trees for the creation of a data-driven decision algorithm, integrated with expert's clinical feedback. RESULTS: Three hundred and seventy-seven studies met eligibility criteria, totaling 844 patients and 13 antibodies: amphiphysin, GAD, GlyR, mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, NMDAR, LGI-1, CRMP5/CV2, ANNA-1/Hu, IgLON5, and DPPX. Stiffness/rigidity/spasm spectrum symptoms were more frequently associated with amphiphysin, GAD, and GlyR; ataxia with mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, and ANNA-1/Hu; dyskinesia with NMDAR and paroxysmal movement with LGI1; chorea/choreoathetosis with CRMP5/CV2, IgLON5, and NMDAR; myoclonus with GlyR and DPPX; tremors with ANNA2/Ri and anti-DPPX; and parkinsonism with IgLON5 and NMDAR. Data-driven classification analysis determined the following diagnostic predictions (with probability selection): psychiatric symptoms and dyskinesia predicted NMDAR (71% and 87%, respectively); stiffness/rigidity/spasm and ataxia, GAD (67% and 47%, respectively); ataxia and opsoclonus, ANNA-2/Ri (68%); chorea/choreoathetosis, CRMP5/CV2 (41%). These symptoms remained the top predictors in random forests analysis. The integration with an expert opinion analysis refined the precision of the approach. Breast and lung tumors were the most common tumors. On neuroimaging, cerebellar involvement was associated with GAD and Yo/PCA-1; temporal involvement with Caspr2, LGI-1, ANNA-1/Hu. CONCLUSION: Selected movement disorders are associated with specific anti-neuronal antibodies. The combination of data-driven and expert opinion approach to the diagnosis may assist early management efforts.


Subject(s)
Cerebellar Ataxia , Chorea , Movement Disorders , Autoantibodies , Cell Adhesion Molecules, Neuronal , Humans , Spasm
8.
J Clin Sleep Med ; 18(5): 1263-1270, 2022 05 01.
Article in English | MEDLINE | ID: mdl-34931609

ABSTRACT

STUDY OBJECTIVES: To evaluate the health-related quality of life (HRQoL) in patients with upper airway respiratory syndrome (UARS) and obstructive sleep apnea (OSA) compared to the general population (GP) in Lima, Peru, and to explore the variables associated with differences in HRQoL in patients with UARS. METHODS: This was a retrospective study of medical and polysomnography records from 2009-2014 in a referral sleep medicine center for patients aged 18-64 years. UARS was defined by polysomnography as follows: apnea-hypopnea index < 5 events/h, oxygen saturation ≥ 92%, respiratory effort-related arousal index ≥ 5. HRQoL was assessed using the 36-Item Short Form Survey (version 1) questionnaire validated in Peru. The GP HRQoL was obtained from a population-based survey. Linear and logistic regression analyses were conducted. RESULTS: We reviewed 1,329 polysomnograms and selected 888. UARS and OSA were diagnosed in 93 and 795 participants, respectively. The GP cohort consisted of 641 participants. Total HRQoL mean scores (95% confidence interval) in patients with UARS, patients with OSA, and the GP were 67.4 (63.7-71.1), 66.9 (65.4-68.4), and 82.9 (81.6-84.3), respectively. Patients with UARS and patients with OSA had a 5.5 times (95% confidence interval, 3.3-9.2) and 6.2 times (95% confidence interval, 4.6-8.4) greater probability of having a low total HRQoL score compared to patients in the GP, respectively. In patients with UARS, muscle pain, use of psychotropic medication, obesity, and depression were negatively correlated with the total HRQoL score. CONCLUSIONS: The impact of OSA and UARS on HRQoL is similar between disease groups and markedly worse when compared to the impact in the GP. In patients with UARS, the presence of muscle pain, obesity, female sex, depression, and use of psychotropic medication negatively impacted HRQoL. CITATION: Vizcarra-Escobar D, Duque KR, Barbagelata-Agüero F, Vizcarra JA. Quality of life in upper airway resistance syndrome. J Clin Sleep Med. 2022;18(5):1263-1270.


Subject(s)
Quality of Life , Sleep Apnea, Obstructive , Airway Resistance , Female , Humans , Myalgia , Obesity , Retrospective Studies , Sleep Apnea, Obstructive/diagnosis , Syndrome
9.
Parkinsonism Relat Disord ; 90: 23-26, 2021 09.
Article in English | MEDLINE | ID: mdl-34343875

ABSTRACT

INTRODUCTION: Otological symptoms contribute to the disability of established Parkinson's disease (PD). We sought to evaluate whether prodromal onset may affect PD progression. METHODS: A retrospective cohort design was used to compare time to advanced disease, defined as a Hoehn & Yahr stage ≥3 in consecutive PD patients with history of auditory and/or vestibular symptoms appearing before versus after PD onset. Time from PD onset to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR). RESULTS: After adjusting for age at PD onset, there was a lower risk of progression to advanced disease in patients with prodromal otological symptoms compared to those with otological symptoms after PD onset (HR = 0.34; 95%CI: 0.15-0.75, p = 0.008). This association remained significant after adjusting for age at PD onset and MDS-UPDRS III (HR = 0.25; 95% CI: 0.10-0.63, p = 0.003) and propensity score-adjusted analysis (HR = 0.46; 95% CI: 0.24-0.91, p = 0.025). CONCLUSION: Prodromal otological symptoms might be associated with a reduced risk of motor progression in PD.


Subject(s)
Ear Diseases/diagnosis , Parkinson Disease/physiopathology , Prodromal Symptoms , Time Factors , Aged , Disease Progression , Ear Diseases/etiology , Female , Humans , Male , Middle Aged , Parkinson Disease/complications , Proportional Hazards Models , Retrospective Studies
10.
Eur J Neurol ; 28(12): 3999-4009, 2021 12.
Article in English | MEDLINE | ID: mdl-34296504

ABSTRACT

BACKGROUND AND PURPOSE: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. METHODS: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. RESULTS: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. CONCLUSIONS: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.


Subject(s)
Dystonia , Dystonic Disorders , Adult , Databases, Factual , Dystonia/epidemiology , Dystonic Disorders/complications , Dystonic Disorders/epidemiology , Humans , Tremor/epidemiology , Tremor/etiology
11.
Int J Mol Sci ; 22(14)2021 Jul 07.
Article in English | MEDLINE | ID: mdl-34298918

ABSTRACT

The gold standard for classification of neurodegenerative diseases is postmortem histopathology; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia-ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann-Pick disease Type C. Postmortem evaluation unexpectedly demonstrated neurodegeneration with 4-repeat tau deposition in a distribution diagnostic of progressive supranuclear palsy (PSP). Whole-exome sequencing revealed a new heterozygous variant in TGM6, associated with spinocerebellar ataxia type 35 (SCA35). This novel TGM6 variant reduced transglutaminase activity in vitro, suggesting it was pathogenic. This case could be interpreted as expanding: (1) the PSP phenotype to include a spinocerebellar variant; (2) SCA35 as a tau proteinopathy; or (3) TGM6 as a novel genetic variant underlying a SCA35 phenotype with PSP pathology. None of these interpretations seem adequate. We instead hypothesize that impairment in the crosslinking of tau by the TGM6-encoded transglutaminase enzyme may compromise tau functionally and structurally, leading to its aggregation in a pattern currently classified as PSP. The lessons from this case study encourage a reassessment of our clinicopathology-based nosology.


Subject(s)
tau Proteins/genetics , Female , Humans , Middle Aged , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Phenotype , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/pathology , Supranuclear Palsy, Progressive/genetics , Supranuclear Palsy, Progressive/pathology , Transglutaminases/genetics
12.
Mov Disord ; 36(6): 1392-1400, 2021 06.
Article in English | MEDLINE | ID: mdl-33590555

ABSTRACT

BACKGROUND: In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. OBJECTIVES: To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoMoFA). METHODS: We recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test-retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire. RESULTS: Two hundred subjects and their care-partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1-5]; mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had "item-to-total" correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64-0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy. CONCLUSIONS: The final 27-item self-administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non-motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society.


Subject(s)
Parkinson Disease , Aged , Canada , Humans , Middle Aged , Parkinson Disease/diagnosis , Reproducibility of Results , Severity of Illness Index , Surveys and Questionnaires
13.
Article in English | MEDLINE | ID: mdl-33563813

ABSTRACT

OBJECTIVE: To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. METHODS: Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years), 67.0% women) were prospectively acquired and analysed. HR-QoL (RAND 36-Item Health Survey), severity of depressive symptoms, generalised anxiety (Hospital Anxiety and Depression Scale) and social anxiety (Liebowitz Social Anxiety Scale) were assessed. Dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale) and dystonic tremor were examined. Statistical predictors of HR-QoL were calculated using saturated path analysis. RESULTS: Reduced HR-QoL was strongly associated with the degree of depressive symptoms and generalised and social anxiety (8/8 RAND 36 subscales, p≤0.001). Increased dystonia severity was associated with worse physical functioning, physical and emotional role functioning and social functioning (all p≤0.001). The presence of tremor correlated with worse physical functioning and pain (all p≤0.006). Younger age was associated with reduced emotional well-being and vitality (all p≤0.006). There were no HR-QoL differences between sexes. CONCLUSION: HR-QoL in isolated dystonia is strongly associated with psychiatric and physical features. While current standard of care focus on motor aspects of dystonia, comprehensive care should address both physical and mental aspects of health.

14.
J Parkinsons Dis ; 11(2): 857-864, 2021.
Article in English | MEDLINE | ID: mdl-33579875

ABSTRACT

BACKGROUND: Urinary dysfunction and constipation, manifestations of pelvic floor dysfunction are common sources of disability and impaired quality of life in women with Parkinson's disease (PD). OBJECTIVE: We sought to evaluate the pelvic floor health amongst women with PD and their reporting of bladder and bowel symptoms. METHODS: We surveyed women with PD and age-matched controls about pelvic floor health using validated questionnaires. All participants completed the Pelvic Floor Disability Index (PFDI-20), the Pelvic Floor Impact Questionnaire (PFIQ-7) and the Patient-Reported Outcomes Measurement Information System (PROMIS) short form version 2.0 Cognitive Function 8a. Additionally, PD patients underwent the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scale and the Montreal Cognition Assessment (MoCA). RESULTS: Women with PD (n = 59; age, 70.4±8.6 years, PROMIS cognitive score, 52.0±7.8) self-reported urinary symptoms to a greater extent than controls (n = 59; age, 70.2±8.7 years, PROMIS cognitive score, 51.0±10) (68% vs 43%, p < 0.01). The difference was mirrored by higher (worse) scores on both PFDI-20 (35.4 vs 15.6; p = 0.01) and PFIQ-7 (4.8 vs 0; p < 0.01) for PD women compared to controls. Only 63% of all participants with self-reported pelvic floor symptoms had previously reported these symptoms to a health care provider. There was no difference in utilization of specialty care between the two groups (30% vs 46%, p = 0.2). CONCLUSION: Pelvic floor dysfunction, more common amongst women with PD, is underreported and undertreated. Our study identifies a key gap in care of women with PD.


Subject(s)
Parkinson Disease , Pelvic Floor , Aged , Constipation , Female , Humans , Middle Aged , Parkinson Disease/complications , Parkinson Disease/epidemiology , Quality of Life , Surveys and Questionnaires
15.
Cerebellum ; 20(1): 134-139, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32888184

ABSTRACT

We report a 52-year-old woman presenting with autosomal dominant progressive cerebellar ataxia and familial hemiplegic migraine type 1 whose genetic evaluation, negative for spinocerebellar ataxia (SCA) types 1, 2, 3, and 6, revealed instead a heterozygous pathogenic missense mutation in CACNA1A (NM_001127221:c.1748G > A:p.Arg583Gln). A systematic literature review showed that Arg583Gln is associated predominantly with progressive ataxia combined with episodic disorders (overwhelmingly hemiplegic migraine) whereas Thr666Met, the other most common CACNA1A missense mutation, with a combination of progressive ataxia and episodic disorders in half the cases and episodic disorders only in the other half. While uncertainties remain in the genotype-phenotype correlation of all CACNA1A mutations, the accumulated evidence suggests that that the co-occurrence of hemiplegic migraine and autosomal dominant progressive cerebellar ataxia should guide the clinician to test for CACNA1A missense mutation rather than CAG expansions or truncating mutations.


Subject(s)
Calcium Channels/genetics , Cerebellar Ataxia/etiology , Cerebellar Ataxia/genetics , DNA Repeat Expansion/genetics , Migraine Disorders/complications , Migraine Disorders/genetics , Mutation, Missense/genetics , Cerebellar Ataxia/complications , Female , Genotype , Humans , Middle Aged , Phenotype
16.
Am J Med Genet C Semin Med Genet ; 184(4): 876-884, 2020 12.
Article in English | MEDLINE | ID: mdl-33084218

ABSTRACT

The genetic and phenotypic heterogeneity of neurogenetic diseases forces patients and their families into a "diagnostic odyssey." An increase in the variability of genetic disorders and the corresponding gene-disease associations suggest the need to periodically re-evaluate the significance of variants of undetermined pathogenicity. Here, we report the diagnostic and clinical utility of Targeted Gene Panel Sequencing (TGPS) and Whole Exome Sequencing (WES) in 341 patients with suspected neurogenetic disorders from centers in Buenos Aires and Cincinnati over the last 4 years, focusing on the usefulness of reinterpreting variants previously classified as of uncertain significance. After a mean of ±2years (IC 95:0.73-3.27), approximately 30% of the variants of uncertain significance were reclassified as pathogenic. The use of next generation sequencing methods has facilitated the identification of both germline and mosaic pathogenic variants, expanding the diagnostic yield. These results demonstrate the high clinical impact of periodic reanalysis of undetermined variants in clinical neurology.


Subject(s)
High-Throughput Nucleotide Sequencing , Humans , Exome Sequencing
17.
Rev. neuro-psiquiatr. (Impr.) ; 82(4): 242-257, oct.-dic 2019. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1144847

ABSTRACT

La Esclerosis Múltiple (EM) es una enfermedad crónica del sistema nervioso central, para la cual aún no hay una cura definitiva; sin embargo, existe una diversa variedad de terapias con el objetivo de modificar el curso natural de la enfermedad, que promueve la inclusión constante de nuevas estrategias terapéuticas. Objetivo: La Sociedad Peruana de Neurología, por encargo del Ministerio de Salud, convocó a un comité de expertos con el objetivo de elaborar una guía de práctica clínica para el diagnóstico y tratamiento de EM. Método: Se realizó una búsqueda y evaluación de guías de práctica clínica bajo la metodología AGREE II, escogiendo como modelo la Guía de Práctica Clínica Catalana. Las preguntas clínicas no concernientes al tratamiento fueron resueltas a través de revisión sistemática. Las preguntas clínicas de tratamiento se diseñaron bajo el formato PICO y se resolvieron con un meta-análisis de ensayos clínicos disponibles hasta agosto del 2017, tomando en consideración las terapias aprobadas por DIGEMID hasta enero del 2017. Las recomendaciones finales fueron elaboradas mediante el método Delphi modificado con un consenso de al menos 80% de los miembros de su comité. Finalmente se realizó una revisión externa del manuscrito por expertos internacionales en EM. Resultados: Se formularon 18 preguntas clínicas y 21 recomendaciones para el manejo, incluyendo algoritmos terapéuticos.


Multiple Sclerosis (MS) is a chronic disease of the central nervous system, for which there is still no definitive cure; but there is a diverse variety of therapies with the objective of modifying the course of the disease, which promotes the constant inclusion of new therapeutic strategies. Objective: The Peruvian Society of Neurology, as requested by the Peruvian Health Ministry, convened a committee of experts with the purpose of elaborating a clinical practice guideline for the diagnosis and treatment of MS. Method: Clinical practice guidelines were searched and evaluated according to the AGREE II methodology, choosing the Catalan Clinical Practice Guide as a model. The clinical questions not related to treatment were solved through a systematic review. The clinical treatment questions were assessed under the PICO format and were solved with a meta-analysis of clinical trials available until August 2017, considering the therapies approved by DIGEMID until January 2017. The final recommendations were elaborated using the modified Delphi method with a consensus of at least 80% of the members of its committee. Finally, an external revision of the manuscript was made by international experts in MS. Results: Eighteen clinical questions and twenty-one recommendations for management were developed, including therapeutic algorithms.

18.
Am J Trop Med Hyg ; 101(3): 636-640, 2019 09.
Article in English | MEDLINE | ID: mdl-31309921

ABSTRACT

Children in the Peruvian Amazon Basin are at risk of soil-transmitted helminths (STH) infections. This study aimed to determine the prevalence of STH infection in children from a rural Amazonian community of Peru and to elucidate epidemiological risk factors associated with its perpetuation while on a school-based deworming program with mebendazole. Stool samples of children aged 2-14 years and their mothers were analyzed through direct smear analysis, Kato-Katz, spontaneous sedimentation in tube, Baermann's method, and agar plate culture. A questionnaire was administered to collect epidemiological information of interest. Among 124 children, 25.8% had one or more STH. Individual prevalence rates were as follows: Ascaris lumbricoides, 16.1%; Strongyloides stercoralis, 10.5%; hookworm, 1.6%; and Trichuris trichiura, (1.6%). The prevalence of common STH (A. lumbricoides, T. trichiura, and hookworm) was higher among children aged 2-5 years than older children (31.6% versus 12.8%; P = 0.01). In terms of sanitation deficits, walking barefoot was significantly associated with STH infection (OR = 3.28; CI 95% = 1.11-12.07). Furthermore, STH-infected children more frequently had a mother who was concomitantly infected by STH than the non-STH-infected counterpart (36.4% versus 14.1%, P = 0.02). In conclusion, STH infection is highly prevalent in children from this Amazonian community despite routine deworming. Institutional health policies may include hygiene and sanitation improvements and screening/deworming of mothers to limit the dissemination of STH. Further studies are needed to address the social and epidemiological mechanics perpetuating these infections.


Subject(s)
Feces/parasitology , Helminthiasis/epidemiology , Helminthiasis/transmission , Rural Population , Soil/parasitology , Adolescent , Animals , Anthelmintics/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Mebendazole/therapeutic use , Mothers , Peru/epidemiology , Prevalence , Risk Factors , Sanitation
19.
Early Hum Dev ; 130: 109-115, 2019 03.
Article in English | MEDLINE | ID: mdl-30743197

ABSTRACT

OBJECTIVE: To evaluate the combined prognostic value of neurological examination, head circumference and cranial ultrasound for neurodevelopmental delay (NDD) in very low birth weight (VLBW, <1500 g) preterm infants. METHODS: Prospective follow-up study. Preterm infants with VLWB were assessed for NDD using the Mullen Scales of Early Learning test at 24 months of corrected age. Abnormal neurological examination (≥2 deviant items of Hammersmith neurological examination), microcephaly and major ultrasound abnormalities, each performed at term age, were evaluated as predictors of NDD in a multivariable Poisson model. RESULTS: 35/132 infants (26.5%) had NDD. In the multivariable analysis, microcephaly (RR, 3.2; 95% CI, 1.6-6.7) and major ultrasound abnormalities (RR, 2.7; 95% CI, 1.3-5.7) were associated to NDD. The combination of the two tests showed the highest positive predictive value (100%; 95% CI, 51%-100%), while the combination of normal neurological examination, no major US findings and normal head size at term showed the highest negative predictive value (89%; 95% CI, 78%-95%). The maximum under receiver operating characteristic curve area was for microcephaly or major ultrasound abnormalities (AUC 0.74 (0.65-0.83)). CONCLUSION: The combination of head circumference, cranial ultrasound and neurological examination at term age is useful to predict NDD in VLBW preterm infants.


Subject(s)
Developmental Disabilities/diagnosis , Infant, Very Low Birth Weight/growth & development , Brain/diagnostic imaging , Brain/pathology , Developmental Disabilities/epidemiology , Female , Humans , Infant, Newborn , Male , Neurologic Examination/standards , Predictive Value of Tests , Ultrasonography/standards
20.
Epilepsy Res ; 145: 145-152, 2018 09.
Article in English | MEDLINE | ID: mdl-30007239

ABSTRACT

OBJECTIVE: Discordances between imaging findings of parenchymal neurocysticercosis and seizure expression have been reported, and as such the possibility that neurocysticercosis and seizures may frequently coexist by chance has been raised. In this study, we evaluate the topographic relationship between seizure foci based on semiology and electroencephalography with the location of parenchymal neurocysticercotic lesions. METHODS: Seizure information, neuroimaging (computed tomography and magnetic resonance imaging [MRI]) and electroencephalographic data from three randomized clinical trials of individuals with parenchymal neurocysticercosis and focal seizures were analyzed. Blinded epileptologists defined a potential seizure onset zone and a symptomatogenic zone for each individual based on semiology. The topographic relationship between semiology, either lesion location or areas of perilesional edema on baseline MRI, and electroencephalographic abnormalities were assessed. RESULTS: Fifty-eight patients with one or two parenchymal neurocysticercotic lesions were included in this study. From them, 50 patients (86%; 95% CI, 75%-93%) showed a clinical-topography relationship with the potential seizure onset zone, and 44 (76%) also with the symptomatogenic zone. From the eight patients with no topographic relationship, five had focal seizures 30 days before or after the baseline MRI and showed perilesional edema. All of these five patients showed a clinical-topography relationship between such seizures and an area of perilesional edema, making a total of 55 patients (95%; 95% CI, 85%-99%) with clinical-topography relationship when perilesional edema is considered. Most patients with focal epileptiform discharges (7/8, 88%) had a topographic association between electroencephalographic focality, the potential seizure onset zone and a cysticercotic lesion. CONCLUSION: Seizure semiology and focal epileptiform discharges are topographically related to neurocysticercotic lesions in most patients. These data strongly support seizure origin in the cortex surrounding these lesions.


Subject(s)
Brain/pathology , Neurocysticercosis/diagnostic imaging , Seizures/diagnostic imaging , Adolescent , Adult , Aged , Antiparasitic Agents/therapeutic use , Brain/diagnostic imaging , Brain/physiopathology , Electroencephalography , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurocysticercosis/drug therapy , Neurocysticercosis/physiopathology , Randomized Controlled Trials as Topic , Retrospective Studies , Seizures/physiopathology , Tomography Scanners, X-Ray Computed , Young Adult
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