Speech Symptoms Research Articles

Progression of Motor Speech Function in Speakers With Primary Progressive Apraxia of Speech.

Speakers with primary progressive apraxia of speech (PPAOS) have an insidious onset of motor speech planning/programming difficulties. As the disease progresses, the apraxia of speech (AOS) becomes more severe and a co-occurring dysarthria often emerges. Here, longitudinal data from speakers with phonetic- and prosodic-predominant PPAOS are used to characterize the progression of their motor speech impairment, including the development of dysarthria and mutism. Data are presented from 52 speakers who had PPAOS at enrollment (i.e., progressive AOS in the absence of aphasia, cognitive, or other neurologic symptoms). Twenty-one had predominantly phonetic features, whereas 31 had primarily prosodic features. All participants underwent a comprehensive motor speech evaluation at their enrollment visit and each annual return visit, with a median of three visits per participant. Almost 25% of the speakers with PPAOS presented with dysarthria at their enrollment visit (median disease duration of 3.65 years), whereas more than 70% of them had developed dysarthria by their last visit (median disease duration of 6.85 years). Neither the likelihood to develop dysarthria nor the disease duration at which it was detected differed significantly between the phonetic and prosodic groups. However, muteness emerged sooner for speakers with phonetic-predominant PPAOS; the median disease duration at which they became mute was 1.5 years shorter than for their prosodic counterparts. Clinically, these results facilitate more accurate prognostication of motor speech symptoms in speakers with PPAOS, allowing for timely introduction of alternative means of communication. The results also support the differentiation between progressive AOS and dysarthria as distinct motor speech disorders that often co-occur in these individuals.

Prospective long-term follow-up after grommet insertion: Hearing and functional health outcomes in children

ObjectivesTo assess hearing levels and functional health outcomes of children two years after routine grommet surgery with standard care follow-up (discharge to General Practitioner (GP) care or Ear Nose and Throat (ENT) clinic appointment at 4–8 weeks). MethodsProspective cohort study of 89 children (average age of 7.98 years) recalled for audiological assessment 2 years after grommet surgery in a large ENT outpatient service in South Auckland, New Zealand. Functional health was assessed using parent-reported responses to the OMQ20 questionnaire. Results46 (51.7 %) children had hearing loss in at least one ear with 28 (31.5 %) children having bilateral hearing loss. Māori children had statistically higher odds compared to non-Māori children (odds ratio 5.491, p = .003) to have bilateral hearing loss after controlling for age, household deprivation, gender, season, and mode of follow-up. Most parents reported concerns with their child's hearing, speech, attention-seeking behaviours, and nasal symptoms, but not ear problems. Bilateral hearing loss (p < .001) was found to significantly predict functional health status (total OMQ20 score). ConclusionsThe high prevalence of hearing loss and functional health concerns suggest that the standard follow-up care is not adequately managing children after routine grommet insertion. Māori children are disproportionately impacted, and post-grommet follow-up schedules must consider individualised approaches to address these inequities in outcomes.

Rapid Assay Diagnostic for Acute Stroke Recognition (RADAR): study protocol for a diagnostic accuracy study

IntroductionLarge-vessel occlusion (LVO) stroke is effectively treated by time-critical thrombectomy, a highly specialised procedure only available in a limited number of centres. Many patients with suspected stroke are admitted to...

Hybrid SPEAK OUT! protocol improves aerodynamic measurements and PROMs in Parkinson's disease.

SPEAK OUT! has been shown to enhance various aspects of voice such as intensity, prosody, voice quality and perception of voice. However, their impacts on expiration and communication effectiveness have not yet been evaluated. This study aimed to evaluate the effectiveness of the Hybrid SPEAK OUT! method on aerodynamic measurements and patient-reported outcome measures (PROMs) in individuals with Parkinson's disease (PD). This study included 157 participants with PD who underwent an intensive 8-week multidisciplinary treatment program. The Hybrid SPEAK OUT! method consisted of three sessions per week, including two group sessions and one individual treatment session. Voice-related aerodynamic measures included maximum phonation time (MPT), vocal cord function using the S/Z ratio, and expiratory flow measures including peakexpiratoryflow (PEF) and peak cough flow (PCF). Two PROMs were included: the Hebrew version of the voice handicap index-10 and communication effectiveness questionnaire. The results of 111 participants were analysed. MPT duration increased, PEF and PCF increased, and better scores were found in PROMs. These findings would appear to support the effectiveness of the Hybrid SPEAK OUT! methods improving function, activity and participation in individuals with PD. However, further research is needed. What is already known on the subject Prior research has demonstrated the effectiveness of behavioral therapies, including the SPEAK OUT! program, in managing speech symptoms in individuals with Parkinson's disease (PD). These therapies have shown improvements in voice intensity, fundamental frequency, voice quality, and voice perception. However, the impact on aerodynamic measures, expiratory flow, and patient-reported outcome measures has not been extensively studied. What this paper adds to existing knowledge This study adds to the existing knowledge by demonstrating that a Hybrid SPEAK OUT! approach, can lead to improvements in aerodynamic measures, including maximum phonation time (MPT), expiratory and cough peak flow. In terms of motor learning, we found that two non-speech exhalation-related tasks that were not directly trained improved following the intensive speech training protocol. Furthermore, it shows positive changes in patient-reported outcome measures, with reduced voice-related disability and improved communication efficiency. What are the potential or actual clinical implications of this work? The findings of this study have important clinical implications for the management of speech symptoms in individuals with PD. The Hybrid SPEAK OUT! program, which combines group and individual sessions, can effectively improve voice, aerodynamic measurements and patient-reported outcome measures (PROMs), ultimately enhancing the overall quality of life for patients. These findings support the effectiveness of the Hybrid SPEAK OUT! methods for improving function, activity, and participation in individuals with PD.

The relationship of rate and pause features to the communicative participation of people living with ALS.

Many people living with amyotrophic lateral sclerosis (PALS) report restrictions in their day-to-day communication (communicative participation). However, little is known about which speech features contribute to these restrictions. This study evaluated the effects of common speech symptoms in PALS (reduced overall speaking rate, slowed articulation rate, and increased pausing) on communicative participation restrictions. Participants completed surveys (the Communicative Participation Item Bank-short form; the self-entry version of the ALS Functional Rating Scale-Revised) and recorded themselves reading the Bamboo Passage aloud using a smartphone app. Rate and pause measures were extracted from the recordings. The association of various demographic, clinical, self-reported, and acoustic speech features with communicative participation was evaluated with bivariate correlations. The contribution of salient rate and pause measures to communicative participation was assessed using multiple linear regression. Fifty seven people living with ALS participated in the study (mean age = 61.1 years). Acoustic and self-report measures of speech and bulbar function were moderately to highly associated with communicative participation (Spearman rho coefficients ranged from rs = 0.48 to rs = 0.77). A regression model including participant age, sex, articulation rate, and percent pause time accounted for 57% of the variance of communicative participation ratings. Even though PALS with slowed articulation rate and increased pausing may convey their message clearly, these speech features predict communicative participation restrictions. The identification of quantitative speech features, such as articulation rate and percent pause time, is critical to facilitating early and targeted intervention and for monitoring bulbar decline in ALS.

Clinical Predictors of Acute Ischemia in Patients with Low-Risk Neurological Deficits.

Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability. We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel's c-statistic. In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01-1.05), motor (OR 2.18, 95%CI 1.27-3.65) or speech symptoms (OR 2.53, 95%CI 1.28-4.80), and no previous identical event (OR 1.75, 95%CI 1.07-2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32-0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14-0.69), normal exam (OR 0.55, 95%CI 0.35-0.85) and resolved symptoms (OR 0.49, 95%CI 0.30-0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69-0.77). Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.

Functional Neurological Disorder Presenting After Concussion: A Retrospective Case Series.

Although a majority of individuals recover from a concussion within weeks of the index injury, a substantial minority of patients report persistent postconcussion symptoms. Some of these symptoms may reflect a diagnosis of functional neurological disorder (FND). The authors evaluated the relationship between persistent postconcussion symptoms and FND symptoms. In this retrospective chart review, the authors characterized demographic and clinical information from 50 patients with a confirmed diagnosis of FND whose functional neurological symptoms started after a concussion. Patients who developed FND after a concussion had high rates of baseline risk factors for both persistent postconcussion symptoms and FND. After the concussive event, functional neurological symptoms presented abruptly or developed insidiously over time. Functional neurological symptoms ranged widely and included gait symptoms, seizures, speech and language symptoms, weakness, sensory symptoms, tremors, and vision and oculomotor symptoms. Functional neurological symptoms can arise after a concussion. FND should be considered in the differential diagnosis of individuals presenting with neurological symptoms beginning after a concussion. By failing to recognize functional symptoms, clinicians may inadvertently reinforce negative health-related beliefs regarding a patient's injured brain.

Immunization with Sez6L2 protein mimics the human condition of late-onset cerebellar ataxia with associated Sez6L2 autoantibodies in mice

Abstract Sez6L2 autoantibodies have been identified in a subset of human patients with progressive cerebellar ataxia. Sez6L2 is a transmembrane protein expressed by most neurons, including Purkinje cells and granular cells of the cerebellum. Patients with Sez6L2 autoantibodies present with gait ataxia, slurred speech, and ocular motor symptoms. Some patients also develop limb ataxia and cognitive deficits. These case studies have led to the hypothesis that autoimmunity against Sez6L2 can directly cause cerebellar damage leading to ataxia. We tested whether C57BL/6J mice immunized against Sez6L2 protein develop ataxia symptoms. We also investigated the systemic immune response against Sez6L2 and whether there was increased immune cell infiltration into the brain. We found that mice immunized with Sez6L2 generated significant levels of anti-Sez6L2 antibodies, in addition to a significant population of Sez6L2-specific CD4 and CD8 T cells. Furthermore, these mice had increased CD4+ T cell infiltration into the brain. The Sez6L2 immunized mice also exhibited mild mobility impairments in open field and wire grid walk assays. Overall, our results demonstrate that an autoimmune response to Sez6L2 in mice can lead to mobility impairments and pathology consistent with human patients who develop cerebellar ataxia associated with Sez6L2 autoantibodies. This new mouse model should be useful for mechanistic studies on a poorly understood autoimmune disease.

Short-term effects of transcranial direct current stimulation on motor speech in Parkinson’s disease: a pilot study

Introduction: Hypokinetic dysarthria (HD) is a common motor speech symptom of Parkinson’s disease (PD) which does not respond well to PD treatments. We investigated short-term effects of transcranial direct current stimulation (tDCS) on HD in PD using acoustic analysis of speech. Based on our previous studies we focused on stimulation of the right superior temporal gyrus (STG) - an auditory feedback area. Methods: In 14 PD patients with HD, we applied anodal, cathodal and sham tDCS to the right STG using a cross-over design. A protocol consisting of speech tasks was performed prior to and immediately after each stimulation session. Linear mixed models were used for the evaluation of the effects of each stimulation condition on the relative change of acoustic parameters. We also performed a simulation of the mean electric field induced by tDCS. Results: Linear mixed model showed a statistically significant effect of the stimulation condition on the relative change of median duration of silences longer than 50 ms (p = 0.015). The relative change after the anodal stimulation (mean = -5.9) was significantly lower as compared to the relative change after the sham stimulation (mean = 12.8), p = 0.014. We also found a correlation between the mean electric field magnitude in the right STG and improvement of articulation precision after anodal tDCS (R = 0.637; p = 0.019). Conclusions: The exploratory study showed that anodal tDCS applied over the auditory feedback area may lead to shorter pauses in a speech of PD patients.

Therapeutic Singing and Semi-Occluded Vocal Tract Exercises for Individuals with Parkinson's Disease: A Randomized Controlled Trial of a Single Session Intervention.

Individuals with Parkinson's disease (PD) experience speech and voice-related symptoms that diminish communication and quality of life. Semi-occluded vocal tract (SOVT) exercises are targeted interventions that, when combined with the positive psychosocial benefits of therapeutic group singing (TGS), may affect outcomes. The purpose of this study was to explore the effectiveness of SOVT exercises, specifically straw phonation combined with TGS, to improve voice quality and mood for individuals with PD. We used a true experimental pretest-posttest between-subjects design (i.e., randomized controlled trial) facilitated by a board-certified music therapist. All participants (N = 27) were randomly assigned to one of three groups (a) straw phonation combined with TGS (SP + TGS, n = 10), (b) TGS (n = 10), and (c) speaking-only control group (n = 7). Participants completed voice recordings for acoustic measures and the Visual Analogue Mood Scale for mood analysis before and after a 30-min intervention. The results demonstrated significant improvement in voice quality evidenced by decreasing Acoustic Voice Quality Index scores following a single session for both SP + TGS and TGS intervention groups when compared to the control. Happiness scores improved in the experimental groups when compared to control. Although not statistically significant, participants in the experimental groups (SP + TGS, TGS) demonstrated better mean mood scores on happiness, anxiety, and angry when compared to control, indicating a positive psychological response to the singing interventions. Overall, this study indicated the effectiveness of SP + TGS and TGS as promising therapeutic interventions for voice quality and mood in individuals with PD.

Automated analysis of speech as a marker of sub-clinical psychotic experiences.

Automated speech analysis techniques, when combined with artificial intelligence and machine learning, show potential in capturing and predicting a wide range of psychosis symptoms, garnering attention from researchers. These techniques hold promise in predicting the transition to clinical psychosis from at-risk states, as well as relapse or treatment response in individuals with clinical-level psychosis. However, challenges in scientific validation hinder the translation of these techniques into practical applications. Although sub-clinical research could aid to tackle most of these challenges, there have been only few studies conducted in speech and psychosis research in non-clinical populations. This work aims to facilitate this work by summarizing automated speech analytical concepts and the intersection of this field with psychosis research. We review psychosis continuum and sub-clinical psychotic experiences, and the benefits of researching them. Then, we discuss the connection between speech and psychotic symptoms. Thirdly, we overview current and state-of-the art approaches to the automated analysis of speech both in terms of language use (text-based analysis) and vocal features (audio-based analysis). Then, we review techniques applied in subclinical population and findings in these samples. Finally, we discuss research challenges in the field, recommend future research endeavors and outline how research in subclinical populations can tackle the listed challenges.

Rare case in Somalia: Fahr’s syndrome

Introduction and importance: Fahr’s syndrome is primarily familial, autosomal dominant, and genetically diverse. Basal ganglia calcification that is bilaterally symmetrical is a hallmark of this illness. Although the specific origins of this illness are unknown, it may be brought on by problems with calcium metabolism, infections, toxins, hereditary factors, hypoparathyroidism, and pseudohypoparathyroidism. The prevalence of this syndrome is less than 0.5%. Case presentation: An 11-year-old female comes to the Emergency Department with her parents complaining of high-grade fever and convulsions for 1 week. Convulsion, which is a generalized tonic–clonic seizure, duration was ~5 min and associated with urinary incontinence and biting tongue. On examination, the patient was confused and irritable. Vital signs were normal; there is weakness in the right arm and right leg, associated with irregular movement. There was alternation in her level of consciousness, slurring of speech, and psychiatric symptoms. Another aspect of the neurological examination and systems was normal, and there was no meningeal irritation. Clinical discussion: The pathogenesis of Fahr’s syndrome is not completely known. The calcification is caused by flaws in the transport of radioactive particles and tissue damage caused by free radicals. Bilateral calcification found on a computed tomography (CT) scan of the brain, autosomal dominant inheritance, the absence of any infection, drugs, or toxins, the absence of mitochondrial dysfunction, and the presence of progressive neurological dysfunction is the clinical criteria for diagnosing Fahr’s syndrome. Conclusion: Basal ganglia calcification that is bilaterally symmetrical is a hallmark of Fahr’s syndrome. CT scans are the gold standard for conclusively diagnosing Fahr’s syndrome.

Digital assessment of speech in Huntington disease.

Speech changes are an early symptom of Huntington disease (HD) and may occur prior to other motor and cognitive symptoms. Assessment of HD commonly uses clinician-rated outcome measures, which can be limited by observer variability and episodic administration. Speech symptoms are well suited for evaluation by digital measures which can enable sensitive, frequent, passive, and remote administration. We collected audio recordings using an external microphone of 36 (18 HD, 7 prodromal HD, and 11 control) participants completing passage reading, counting forward, and counting backwards speech tasks. Motor and cognitive assessments were also administered. Features including pausing, pitch, and accuracy were automatically extracted from recordings using the BioDigit Speech software and compared between the three groups. Speech features were also analyzed by the Unified Huntington Disease Rating Scale (UHDRS) dysarthria score. Random forest machine learning models were implemented to predict clinical status and clinical scores from speech features. Significant differences in pausing, intelligibility, and accuracy features were observed between HD, prodromal HD, and control groups for the passage reading task (e.g., p < 0.001 with Cohen'd = -2 between HD and control groups for pause ratio). A few parameters were significantly different between the HD and control groups for the counting forward and backwards speech tasks. A random forest classifier predicted clinical status from speech tasks with a balanced accuracy of 73% and an AUC of 0.92. Random forest regressors predicted clinical outcomes from speech features with mean absolute error ranging from 2.43-9.64 for UHDRS total functional capacity, motor and dysarthria scores, and explained variance ranging from 14 to 65%. Montreal Cognitive Assessment scores were predicted with mean absolute error of 2.3 and explained variance of 30%. Speech data have the potential to be a valuable digital measure of HD progression, and can also enable remote, frequent disease assessment in prodromal HD and HD. Clinical status and disease severity were predicted from extracted speech features using random forest machine learning models. Speech measurements could be leveraged as sensitive marker of clinical onset and disease progression in future clinical trials.

Novel ABCD1 variant causes phenotype of adrenomyeloneuropathy with cerebral involvement in Ukrainian siblings: first adult hematopoietic stem cell transplantation for ALD in Ukraine: a case report

BackgroundThis article presents a case study of two white male siblings of 24 and 31 years of age of self-reported Ukrainian ethnicity diagnosed with adrenomyeloneuropathy (AMN) associated with a novel splice site mutation in the ABCD1 gene. AMN represents a form of X-linked adrenoleukodystrophy (X-ALD) characterized by demyelination of the spinal cord and peripheral nerves. The case also presents the first adult haematopoietic stem cell transplant (HSCT) for adrenomyeloneuropathy in Ukraine. The rarity of this mutation and its cerebral involvement and the treatment make this case noteworthy and underscore the significance of reporting it to contribute to the existing medical knowledge.Case presentationThe patients of 24 and 31 years initially exhibited progressive gait disturbance, lower extremity pain, and urinary incontinence, with the older sibling experiencing more advanced symptoms of speech, hearing, and vision disturbances. A comprehensive genetic analysis identified an unreported splice site mutation in exon 3 of the ABCD1 gene, leading to the manifestation of AMN. The inheritance pattern was consistent with X-linked recessive transmission. The article also outlines the clinical features, magnetic resonance imaging (MRI), and nerve conduction study (NCS) findings. Moreover, it discusses the genetic profile of the affected individuals and female carriers within the family. The younger sibling underwent HSCT, which was complicated by mediastinal lymph node and lung tuberculosis, adding to the complexity of managing adult ALD patients.ConclusionsThis report emphasizes the importance of genetic testing in diagnosing and comprehending the underlying mechanisms of rare genetic disorders, such as AMN with cerebral involvement. The identification of a novel splice site mutation expands our understanding of the genetic landscape of this condition. Additionally, the challenges and complications encountered during the hematopoietic stem cell transplant procedure underscore the need for cautious consideration and personalized approaches in adult ALD patients.

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients

BackgroundDBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. ObjectiveTo parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. MethodsWe performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. ResultsFirst, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. ConclusionsSTN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features.

Presenting Symptoms and Diffusion-Weighted MRI Positivity by Time After Transient Neurologic Events: A Pooled Analysis of 3 Cohort Studies

The association between focal vs nonfocal presenting symptom and diffusion-weighted imaging (DWI) positivity in relation to onset-to-imaging time in patients with transient neurologic events remains unclear. We hypothesize that episodes consisting of focal symptoms would have proportionally higher DWI-positive imaging at later onset-to-imaging times. Patients with transient neurologic symptoms and a normal neurologic examination who had DWI in the combined data set of 3 cohort studies were included. We used logistic regression models to evaluate the association between each type of presenting symptom (motor weakness, speech impairment, sensory symptoms, vision loss, diplopia, gait instability, dizziness, headache, presyncope, and amnesia) and DWI positivity after adjusting for clinical variables (age, sex, history of stroke, dyslipidemia, coronary artery disease, atrial fibrillation, symptoms duration [<10, 10-59, ≥60 minutes, or unclear], and study source). We stratified the results by onset-to-imaging time categories (<6 hours, 6-23 hours, and ≥24 hours). Of the total 2,411 patients (1,345 male, median age 68 years), DWI-positive lesions were detected in 598 patients (24.8%). The prevalence of DWI positivity was highest in those with motor weakness (34.7%), followed by speech impairment (33.5%). In a multivariable analysis, the presence of motor weakness, speech impairment, and sensory symptoms was associated with DWI positivity, while vision loss and headache were associated with lower odds of DWI positivity, but nevertheless had 13.6% and 15.3% frequency of DWI positive. The odds of being DWI positive varied by onset-to-imaging time categories for motor weakness, with greater odds of being DWI positive at later imaging time (<6 hours: odds ratio [OR] 1.25, 95% confidence interval [CI] 0.84-1.87; 6-23 hours: OR 2.24, 95% CI 1.47-3.42; and ≥24 hours: OR 2.42, 95% CI 1.74-3.36; interaction p = 0.033). Associations of other symptoms with DWI positivity did not vary significantly by time categories. We found that onset-to-imaging time influences the relationship between motor weakness and DWI positivity in patients with transient neurologic events. Compared with motor, speech, and sensory symptoms, visual or nonfocal symptoms carry a lower but still a substantive association with DWI positivity.

Primary Progressive Aphasia: Losing the Ability to Communicate

Primary progressive aphasia (PPA) is a rare disorder that affects older adults, causing them to slowly lose the ability to communicate. PPA is caused by certain diseases that damage brain cells in areas of the brain that control speech and language. There are three types of PPA, each with unique speech and language symptoms. While there is not currently a “cure” for the diseases that cause PPA, there are a number of ways to support communication and promote quality of life for individuals with PPA, for as long as possible.

Myasthenia gravis in a pediatric patient with Lennox-Gastaut syndrome following responsive neurostimulation device implantation: illustrative case.

Myasthenia gravis (MG) is an autoimmune disorder in which the postsynaptic acetylcholine receptor of the neuromuscular junction is destroyed by autoantibodies. The authors report a case of MG in a pediatric patient who also suffered from Lennox-Gastaut syndrome (LGS) and is one of a limited number of pediatric patients who have undergone placement of a responsive neurostimulation (RNS) device (NeuroPace). A 17-year-old female underwent placement of an RNS device for drug-resistant epilepsy in the setting of LGS. Five months after device placement, the patient began experiencing intermittent slurred speech, fatigue, and muscle weakness. Initially, the symptoms were attributed to increased seizure activity and/or medication side effects. However, despite changing medications and RNS settings, no improvements occurred. Her antiacetylcholine receptor antibodies measured 62.50 nmol/L, consistent with a diagnosis of MG. The patient was then prescribed pyridostigmine and underwent a thymectomy, which alleviated most of her symptoms. The authors share the cautionary tale of a case of MG in a pediatric patient who was treated with RNS for intractable epilepsy associated with LGS. Although slurred speech, fatigue, muscle weakness, and other symptoms might stem from increased seizure activity and/or medication side effects, they could also be due to MG development.

Subthalamic nucleus physiology is correlated with deep brain stimulation motor and non-motor outcomes.

Subthalamic nucleus deep brain stimulation is commonly indicated for symptomatic relief of idiopathic Parkinson's disease. Despite the known improvement in motor scores, affective, cognitive, voice and speech functions might deteriorate following this procedure. Recent studies have correlated motor outcomes with intraoperative microelectrode recordings. However, there are no microelectrode recording-based tools with predictive values relating to long-term outcomes of integrative motor and non-motor symptoms. We conducted a retrospective analysis of the outcomes of patients with idiopathic Parkinson's disease who had subthalamic nucleus deep brain stimulation at Tel Aviv Sourasky Medical Centre (Tel Aviv, Israel) during 2015-2016. Forty-eight patients (19 women, 29 men; mean age, 58 ± 8 years) who were implanted with a subthalamic nucleus deep brain stimulation device underwent pre- and postsurgical assessments of motor, neuropsychological, voice and speech symptoms. Significant improvements in all motor symptoms (except axial signs) and levodopa equivalent daily dose were noted in all patients. Mild improvements were observed in more posterior-related neuropsychological functions (verbal memory, visual memory and organization) while mild deterioration was observed in frontal functions (personality changes, executive functioning and verbal fluency). The concomitant decline in speech intelligibility was mild and only partial, probably in accordance with the neuropsychological verbal fluency results. Acoustic characteristics were the least affected and remained within normal values. Dimensionality reduction of motor, neuropsychological and voice scores rendered six principal components that reflect the main clinical aspects: the tremor-dominant versus the rigidity-bradykinesia-dominant motor symptoms, frontal versus posterior neuropsychological deficits and acoustic characteristics versus speech intelligibility abnormalities. Microelectrode recordings of subthalamic nucleus spiking activity were analysed off-line and correlated with the original scores and with the principal component results. Based on 198 microelectrode recording trajectories, we suggest an intraoperative subthalamic nucleus deep brain stimulation score, which is a simple sum of three microelectrode recording properties: normalized neuronal activity, the subthalamic nucleus width and the relative proportion of the subthalamic nucleus dorsolateral oscillatory region. A threshold subthalamic nucleus deep brain stimulation score >2.5 (preferentially composed of normalized root mean square >1.5, subthalamic nucleus width >3 mm and a dorsolateral oscillatory region/subthalamic nucleus width ratio >1/3) predicts better motor and non-motor long-term outcomes. The algorithm presented here optimizes intraoperative decision-making of deep brain stimulation contact localization based on microelectrode recording with the aim of improving long-term (>1 year) motor, neuropsychological and voice symptoms.

Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. 'Splitting' views propose separate clinical entities: 'primary progressive apraxia of speech' when AoS occurs in the absence of expressive agrammatism, 'progressive agrammatic aphasia' (PAA) in the opposite case, and 'AOS + PAA' when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism. Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a 'left-right' and 'ventral-dorsal' neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.