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Journal of Clinical Pharmacy and... Aug 2021Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as...
WHAT IS KNOWN AND OBJECTIVE
Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as neurotoxicity, which are less frequent and known. The objective of this review was to collect all the reported cases of neurotoxicity associated with acyclovir and valaciclovir published in the literature and characterize their clinical course and interventions.
METHODS
A systematic review of cases was carried out following the guidelines established by "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA). The research was carried out using the PubMed-Medline and Embase databases, between July 1984 and March 2021.
RESULTS AND DISCUSSION
A total of 119 cases with neurotoxicity mainly related to acyclovir (n = 88; 73.9%), followed by valaciclovir (n = 35; 29.4%) were analysed. 49.6% (n = 59) were men with a mean age of 59.5 years ± 21.1 (0.5-88). In 83.3% of the cases, renal impairment was documented and 57.1% (n = 68) with end-stage renal disease. The administered dose was higher than the renal adjustment recommendations in 59.7% of the cases. The global mean of onset of symptoms was 3.1 days ± 4.3 (0.2-28) after the start of antivirals. The mean recovery time was 9.8 days ± 21.7 (0.2-180). 74.4% of the patients had a recovery of ≤7 days, 15.9% between 8 and 15 days and 9.8% > 15 days.
WHAT IS NEW AND CONCLUSION
The neurotoxicity induced by acyclovir and its derivative valacyclovir is a poorly known and rare adverse effect that can occur mainly in patients with advanced age and impaired renal function. The most characteristic symptoms are confusion, altered level of consciousness, hallucinations, agitation and dysarthria. The basis of treatment is the discontinuation of the antiviral, and in some cases, it may require additional clearance by dialysis.
Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Dose-Response Relationship, Drug; Female; Humans; Kidney Function Tests; Male; Middle Aged; Neurotoxicity Syndromes; Renal Insufficiency; Time Factors; Valacyclovir; Young Adult
PubMed: 34146428
DOI: 10.1111/jcpt.13464 -
Stroke Feb 2022Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack.
METHODS
We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were (1) cohort, cross-sectional, case-control, or randomized controlled trial design; (2) admission for (suspicion of) ischemic or hemorrhagic stroke or transient ischemic attack; and (3) comparisons possible between sexes in ≥1 nonfocal or focal acute stroke symptom(s). A random-effects model was used for our analyses. We performed sensitivity and subanalyses to help explain heterogeneity and used the Newcastle-Ottawa Scale to assess bias.
RESULTS
We included 60 studies (n=582 844; 50% women). In women, headache (pooled odds ratio [OR], 1.24 [95% CI, 1.11-1.39]; I=75.2%; 30 studies) occurred more frequently than in men with any type of stroke, as well as changes in consciousness/mental status (OR, 1.38 [95% CI, 1.19-1.61]; I=95.0%; 17 studies) and coma/stupor (OR, 1.39 [95% CI, 1.25-1.55]; I=27.0%; 13 studies). Aspecific or other neurological symptoms (nonrotatory dizziness and non-neurological symptoms) occurred less frequently in women (OR, 0.96 [95% CI, 0.94-0.97]; I=0.1%; 5 studies). Overall, the presence of focal symptoms was not associated with sex (pooled OR, 1.03) although dysarthria (OR, 1.14 [95% CI, 1.04-1.24]; I=48.6%; 11 studies) and vertigo (OR, 1.23 [95% CI, 1.13-1.34]; I=44.0%; 8 studies) occurred more frequently, whereas symptoms of paresis/hemiparesis (OR, 0.73 [95% CI, 0.54-0.97]; I=72.6%; 7 studies) and focal visual disturbances (OR, 0.83 [95% CI, 0.70-0.99]; I=62.8%; 16 studies) occurred less frequently in women compared with men with any type of stroke. Most studies contained possible sources of bias.
CONCLUSIONS
There may be substantive differences in nonfocal and focal stroke symptoms between men and women presenting with acute stroke or transient ischemic attack, but sufficiently high-quality studies are lacking. More studies are needed to address this because sex differences in presentation may lead to misdiagnosis and undertreatment.
Topics: Cohort Studies; Cross-Sectional Studies; Diagnostic Errors; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Sex Characteristics; Stroke; Treatment Outcome
PubMed: 34903037
DOI: 10.1161/STROKEAHA.120.034040 -
Neurosurgical Review Jun 2022Deep brain stimulation (DBS) is a reversible treatment for chorea-acanthocytosis (ChAc). Its safety and efficacy remain elusive due to the low prevalence of ChAc. We... (Review)
Review
Deep brain stimulation (DBS) is a reversible treatment for chorea-acanthocytosis (ChAc). Its safety and efficacy remain elusive due to the low prevalence of ChAc. We aimed to investigate the safety and efficacy of DBS for ChAc by systematically reviewing literature through PubMed and EMBASE. Inclusion criteria were reports on the efficacy or safety of DBS for ChAc and English language articles, and exclusion criteria were other movement disorders, non-human subjects, and studies without original data. Most studies were published as case reports, and we therefore pooled these cases in one cohort. Twenty studies with 34 patients were included. The mean age of symptom onset was 29.3 years (range, 17-48). The median follow-up was 12 months (range, 2-84). Twenty-nine patients underwent GPi-DBS, two received STN-DBS, and one underwent Vop-DBS. Electrodes were implanted into the ventralis oralis complex of the thalamus and the pallidal in two patients. Symptoms seemed to be easier relieved in chorea (88.5%) and dystonia (76.9%) but dysarthria of most patients (85.7%) was no response after DBS. The Unified Huntington's Disease Rating Scale-Motor Score was used to assess the efficacy of DBS in 25 patients; the mean score decreased from 43.2 to 22.3 and the median improvement rate was 46.7%. Of 24 patients with data on adverse events, complications occurred in 9 patients (37.5%; mostly transient and mild events). DBS is a promising treatment for ChAc with satisfactory efficacy and safety based on the review. Pallidal and thalamic DBS have been applied in ChAc; GPi-DBS seems to be more widely used.
Topics: Deep Brain Stimulation; Dystonia; Globus Pallidus; Humans; Neuroacanthocytosis; Treatment Outcome
PubMed: 35020105
DOI: 10.1007/s10143-022-01735-1 -
Neurological Sciences : Official... Mar 2023Deep brain stimulation (DBS) is a common treatment for Parkinson's disease. However, the clinical efficacy of short pulse width DBS (spDBS) compared with conventional... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Deep brain stimulation (DBS) is a common treatment for Parkinson's disease. However, the clinical efficacy of short pulse width DBS (spDBS) compared with conventional DBS (cDBS) is still unknown.
OBJECTIVE
This meta-analysis investigated the effectiveness of spDBS versus cDBS in patients with PD.
METHODS
Four databases (PubMed, Cochrane, Web of Science, and Embase) were independently searched until October 2021 by two reviewers. We utilized the following scales and items: therapeutic windows (TW), efficacy threshold, side effect threshold, Movement Disorder Society-Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off-medication score, Speech Intelligence Test (SIT), and Freezing of Gait Questionnaire (FOG-Q).
RESULTS
The analysis included seven studies with a total of 87 patients. The results indicated that spDBS significantly widened the therapeutic windows (0.99, 95% CI = 0.61 to 1.38) while increasing the threshold amplitudes of side effects (2.25, 95% CI = 1.69 to 2.81) and threshold amplitudes of effects (1.60, 95% CI = 0.84 to 2.36). There was no statistically significant difference in UPDRS part III, SIT, and FOG-Q scores between spDBS and cDBS groups, suggesting that treatment with both cDBS and spDBS may result in similar effects of improved dysarthria and gait disorders.
CONCLUSIONS
Compared with cDBS, spDBS is effective in expanding TW. Both types of deep brain stimulation resulted in improved gait disorders and speech intelligibility.
Topics: Humans; Parkinson Disease; Subthalamic Nucleus; Deep Brain Stimulation; Gait Disorders, Neurologic; Treatment Outcome
PubMed: 36383263
DOI: 10.1007/s10072-022-06484-z -
Neuroanatomical regions associated with non-progressive dysarthria post-stroke: a systematic review.BMC Neurology Sep 2022Dysarthria is a common and persisting sequela to stroke. It can have a negative influence on psychological wellbeing, and quality of life. This systematic review aimed...
BACKGROUND
Dysarthria is a common and persisting sequela to stroke. It can have a negative influence on psychological wellbeing, and quality of life. This systematic review aimed to describe and identify the neuroanatomical regions associated with non-progressive dysarthria following stroke.
METHODS
A systematic search of PubMed, Ovid Medline, CINAHL, Cochrane, Scopus, and ScienceDirect was conducted to identify all relevant articles published in peer-reviewed journals up to December 2021. Following data extraction, the National Institutes of Health (NIH) quality assessment tools were used to evaluate the methodological quality of the included studies.
RESULTS
Out of 2186 papers found in the literature related to dysarthria post-stroke, 24 met the inclusion criteria. Eligible articles assessed 1150 post-stroke subjects. Out of them, 420 subjects had dysarthria from isolated lesions. Regarding dysarthric subjects with ischemic strokes, 153 sustained supratentorial infarctions, while 267 had infratentorial infarctions. The majority had pontine infarctions (n = 142), followed by infarctions in the corona radiata (n = 104), and the cerebellum (n = 64).
CONCLUSION
This systematic review is the first step toward establishing a neuroanatomical model of dysarthria throughout the whole brain. Our findings have many implications for clinical practice and provide a framework for implementing guidelines for early detection and management of dysarthria post-stroke.
Topics: Dysarthria; Humans; Infarction; Ischemic Stroke; Quality of Life; Stroke; United States
PubMed: 36114518
DOI: 10.1186/s12883-022-02877-x -
Journal of Communication Disorders 2023Prosody serves central functions in language processing including linguistic functions (linguistic prosody), like structuring the speech signal. Impairments in... (Review)
Review
A systematic review on production and comprehension of linguistic prosody in people with acquired language and communication disorders resulting from unilateral brain lesions.
BACKGROUND
Prosody serves central functions in language processing including linguistic functions (linguistic prosody), like structuring the speech signal. Impairments in production and comprehension of linguistic prosody have been described for persons with unilateral right (RHDP) or left hemisphere damage (LHDP). However, reported results differ with respect to the characteristics and severities of these impairments AIMS: We conducted a systematic literature review focusing on production and comprehension of linguistic prosody at the prosody-syntax interface (i.e., phrase or sentence level) in LHDP and RHDP.
METHODS & PROCEDURES
In a systematic literature search we included: (i) empirical studies with (ii) adult RHDP and/or LHDP (iii) investigating production and/or comprehension of linguistic prosody at the (iv) phrase or sentence level (v) reporting quantitative data on prosodic measures. We excluded overview papers; studies involving participants with dysarthria, apraxia of speech, foreign accent syndrome, psychiatric diseases, and/or neurodegenerative diseases; studies focusing primarily on emotional prosody; and on lexical stress / word level; studies of which no full text was available and/or that were published in a language other than English. We searched the databases BIOSIS, MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, Cochrane Library, PSYNDEX, PsycINFO and speechBITE, last searched on January 13 2022.We found 2,631 studies without duplicates. We identified 43 studies which were included into our systematic review. For data extraction and synthesis of results, we grouped studies by (i) modality (production vs. comprehension), (ii) function (syntactic structure vs. information structure), and (iii) by experiment task. For production studies, outcome measures were defined as the productive use of the different prosodic cues (lengthening, pause, f0, amplitude). For comprehension studies, performance measures (accuracy and reaction times) were defined as outcome measures. In accordance with the PRISMA 2020 statement (Page et al., 2021), we conducted a quality check to assess study risk of bias. Our review was pre-registered with PROSPERO (CRD42019120308).
OUTCOMES & RESULTS
Of the 43 studies reviewed, 30 studies involved RHDP (n = 309), assessing production in 15 studies and focusing on comprehension of prosody in 16 studies (one study investigated production and comprehension). LHDP (n = 438) were included in 35 studies of which 15 studied production and 21 evaluated comprehension of prosody (one study investigated production and comprehension). Despite the heterogeneity of results in the studies reviewed, our synthesis of results suggests that both LHDP and RHDP show limitations, but no complete impairment, in their production and/or comprehension of linguistic prosody. Prosodic limitations are evident in different areas of processing linguistic prosody, like syntactic disambiguation or the distinction between sentence types. There is a tendency towards more severe limitations in LHDP as compared to RHDP.
CONCLUSIONS
We only included published studies into our review and did not perform an assessment of risk of reporting bias as well as systematic certainty assessments of the outcomes. Despite these limitations, we conclude that both groups show deficits in production and comprehension of linguistic prosody, but neither LHDP nor RHDP are completely impaired in their prosodic processing. This suggests that prosody is a relevant communicative resource for LHDP and RHDP worth being addressed in speech-language-therapy.
Topics: Adult; Humans; Comprehension; Language; Linguistics; Communication Disorders; Brain; Speech Perception
PubMed: 36623377
DOI: 10.1016/j.jcomdis.2022.106298 -
Journal of Clinical Neuroscience :... Nov 2023Hemangioblastomas (HBs) are highly vascular tumors linked to substantial morbidity and mortality. Recently, interventional neuroradiology has evolved rapidly, spurring... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hemangioblastomas (HBs) are highly vascular tumors linked to substantial morbidity and mortality. Recently, interventional neuroradiology has evolved rapidly, spurring interest in preoperative embolization as a possible HB treatment.
PURPOSE
This study evaluates the effectiveness and safety of preoperative embolization in managing HB.
METHODS
Adhering to PRISMA guidelines, this meta-analysis considered randomized and nonrandomized studies meeting specific criteria, encompassing intracranial HB and preoperative embolization. Primary outcomes were preoperative embolization efficacy and safety. Complications were classified as major (cerebellar ischemia, ischemic strokes, intratumoral hemorrhage, subarachnoid hemorrhage) and minor (transient nystagmus, slight facial nerve palsy, nausea, transient dysarthria, hemiparesis, hemisensory impairment, thrombotic complications, extravasation).
RESULTS
Thirteen studies involving 166 patients with preoperative embolization before HB resection were included. Two studies using the Glasgow Outcome Scale (GOS) showed 5 patients with good recovery, 6 with moderate disability, and 3 with severe disability. Major complications occurred in 1% (95% CI: 0% to 3%), and minor complications occurred in 1% (95% CI: 0% to 4%). Intraoperative blood loss during resection was estimated at 464.29 ml (95% CI: 350.63 ml to 614.80 ml).
CONCLUSION
Preoperative embolization holds promise in reducing intraoperative bleeding risk in neurosurgical intracranial HB treatment, primarily due to its low complication rates. Nonetheless, additional research and larger-scale studies are essential to establish its long-term efficacy and safety. These findings highlight preoperative embolization as a valuable tool for HB management, potentially enhancing future patient outcomes.
Topics: Humans; Hemangioblastoma; Embolization, Therapeutic; Neurosurgical Procedures; Preoperative Care; Blood Loss, Surgical; Treatment Outcome; Retrospective Studies
PubMed: 37788533
DOI: 10.1016/j.jocn.2023.09.021 -
Journal of Neurosurgery. Pediatrics Dec 2023Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for...
OBJECTIVE
Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for diagnostic and potentially therapeutic purposes. However, there is no consensus on the safety of biopsy or effect on survival. The authors aimed to characterize neurological risk associated with and the effect of stereotactic biopsy on survival among patients with DIPGs.
METHODS
A systematic review was performed in accordance with PRISMA guidelines to identify all studies examining pediatric patients with DIPG who underwent stereotactic biopsy. The search strategy was deployed in PubMed, Embase, and Scopus. The quality of studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and risk of bias was evaluated with the Cochrane Risk of Bias in Nonrandomized Studies-of Interventions tool. Bibliographic, demographic, clinical, and outcome data were extracted from studies meeting inclusion criteria.
RESULTS
Of 2634 resultant articles, 13 were included, representing 192 patients undergoing biopsy. The weighted mean age at diagnosis was 7.5 years (range 0.5-17 years). There was an overall neurosurgical complication rate of 13.02% (25/192). The most common neurosurgical complication was cranial nerve palsy (4.2%, 8/192), of which cranial nerve VII was the most common (37.5%, 3/8). The second most common complication was perioperative hemorrhage (3.6%, 7/192), followed by hemiparesis (2.1%, 4/192), speech disorders (1.6%, 3/192) such as dysarthria and dysphasia, and movement disorders (1.0%, 2/192). Hydrocephalus was less commonly reported (0.5%, 1/192), and there were no complications relating to wound infection/dehiscence (0%, 0/192) or CSF leak (0%, 0/192). No mortality was specifically attributed to biopsy. Diagnostic yield of biopsy revealed a weighted mean of 97.4% (range 91%-100%). Of the studies reporting survival data, 37.6% (32/85) of patients died within the study follow-up period (range 2 weeks-48 months). The mean overall survival in patients undergoing biopsy was 9.73 months (SD 0.68, median 10 months, range 6-13 months).
CONCLUSIONS
Children with DIPGs undergoing biopsy have mild to moderate rates of neurosurgical complications and no excessive morbidity. With reasonably acceptable surgical risk and high diagnostic yield, stereotactic biopsy of DIPGs can allow for characterization of patient-specific molecular and genetic features that may influence prognosis and the development of future therapeutic strategies.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Glioma; Diffuse Intrinsic Pontine Glioma; Brain Stem Neoplasms; Biopsy
PubMed: 37724839
DOI: 10.3171/2023.7.PEDS22462 -
Journal of Voice : Official Journal of... Jul 2023Hyperkinetic dysarthria is characterized by atypical involuntary movements within the speech mechanism that may affect the respiratory, laryngeal, pharyngeal-oral, or... (Review)
Review
INTRODUCTION
Hyperkinetic dysarthria is characterized by atypical involuntary movements within the speech mechanism that may affect the respiratory, laryngeal, pharyngeal-oral, or velopharyngeal-nasal subsystems and may alter speech production. Although articulatory impairments are commonly considered in hyperkinetic dysarthria, speakers with hyperkinetic dysarthria may also present with changes in voice quality, pitch, and loudness. In approximately 70% of speakers with hyperkinetic dysarthria, these voice alterations are associated with tremor or dystonia. The purpose of this systematic review was to investigate the association between behavioral therapy for tremor or dystonia affecting voice in speakers with hyperkinetic dysarthria and improvement in the functional, perceptual, acoustical, aerodynamic, or endoscopic characteristics of voice.
METHOD
MEDLINE (PubMed), Embase, PsycINFO, and ClinicalTrials.gov online databases were searched in August 2017, December 2018, and April 2020 for relevant studies. The searches provided 4,921 unique records, and six additional unique records were added from other sources. Twelve studies met the criteria for inclusion in the systematic review. Participants who received concurrent medical treatment were included in this review to ensure that the search was inclusive of all relevant studies and informative for typical clinical scenarios.
RESULTS
The most commonly administered treatment ingredient was relaxation training, which was investigated in three of the four studies on tremor and three of the eight studies on dystonia. Of these six studies, only one used an experimental design and administered relaxation training as the only behavioral approach. This single-case experiment reported a significant reduction in participant ratings of tremor severity and interference with activities of daily living, although the speaking subscale reportedly did not improve and oral medications were administered concurrently. In two group studies that tested potential behavioral therapy targets, production of a low pitch improved acoustical measures for participants with essential tremor and improved auditory-perceptual judgments for participants with laryngeal dystonia. Behavioral therapy improved functional, acoustical, and aerodynamic outcomes in participants with laryngeal dystonia who were also receiving botulinum toxin injections in a randomized cross-over study and a non-randomized controlled study. Because one study employed easy onset and breathing exercises, while the other employed loud voice exercises, the mechanism of action for improvement in voice associated with behavioral therapy requires further investigation.
CONCLUSION
This systematic review describes the current evidence for treatment of tremor and dystonia affecting voice in speakers with hyperkinetic dysarthria and highlights the need for future research on behavioral therapy for these disorders.
Topics: Humans; Activities of Daily Living; Behavior Therapy; Dysarthria; Dystonia; Tremor
PubMed: 34112549
DOI: 10.1016/j.jvoice.2021.03.026 -
Expert Opinion on Drug Safety Jul 2022The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically...
INTRODUCTION
The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation.
AREAS COVERED
We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists. The reports described 92 [median 1, range 1-5] cases, documented median age 28 [2.7-78] years. Eighty-one cases described one or more clinical sign of ataxia (present in 96%), dysarthria (63%), and nystagmus (70%). The neurological outcome (in 76 cases): 10 (13%) recovered by 12 months; 55 (72%) suffered residual disability; and 11 (14%) died. Median serum phenytoin concentration (48 cases) was 50 (interquartile range 31-66) mg/L; only three values were below 20 mg/L. The radiological findings included cerebellar atrophy in 41 of 61 patients (67%) with at least one scan.
EXPERT OPINION
Evidence mainly comes from case reports, and is inevitably biased. Most patients with cerebellar dysfunction have phenytoin concentrations above the reference range. Clinical signs of ataxia can persist without radiological evidence of cerebellar atrophy, and cerebellar atrophy is seen without any clinical evidence of cerebellar dysfunction.
Topics: Adult; Ataxia; Atrophy; Cerebellar Ataxia; Cerebellar Diseases; Cerebellum; Humans; Phenytoin
PubMed: 35325581
DOI: 10.1080/14740338.2022.2058487