Network Fingerprint of Stimulation-Induced Speech Impairment in Essential Tremor.

OBJECTIVE: This study was undertaken to gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). METHODS: Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was then validated in a leave-one-out design. RESULTS: Fibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al-Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p < 0.001) of the variance of stimulation-induced change in intelligibility in a leave-one-out analysis. INTERPRETATION: This study demonstrates that SID in essential tremor patients is associated with both motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in essential tremor patients with thalamic DBS. ANN NEUROL 2021;89:315-326.

A 41-year-old female with progressive multifocal leukoencephalopathy after liver transplant.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC virus reactivation. Its occurrence is very rare after solid organ transplantation, especially liver transplantation. We report a patient who received liver transplantation due to liver failure resulting from autoimmune hepatitis and advanced PML presenting with aphasia. A 41-year-old female with a history of liver transplantation who received a usual immunosuppression regimen was admitted with a stroke attack resulting in right hemiplegia 2 months after liver transplantation. Surprisingly, she gradually developed dysarthria and left central facial paresis. A brain MRI showed an abnormal multifocal area with a high T2/flair signal in the deep subcortical white matter of the left hemisphere as well as the splenium of the corpus callosum. PCR evaluation of CSF for JCV was positive while other PCR results were negative. A liver transplant recipient receiving immunosuppressive treatment for a long time could develop PML due to JCV reactivation. Only eight cases of JCV infection were reported after liver transplantation by the time of reporting this case. Unfortunately, there is no definite treatment for PML.

Foix-Chavany-Marie syndrome secondary to bilateral traumatic operculum injury.

This report describes a case of a 62-year-old man who developed Foix-Chavany-Marie syndrome subsequent to traumatic brain injury. The initial presentation of the syndrome was profound loss of voluntary control of orofacial muscles, causing a loss of speech and impairment of swallow. Over subsequent months, a remarkable recovery of these functions was observed. The natural history of FCMS in this case was favourable, with good improvement in function over months. Furthermore, the pattern of bilateral opercular injury was more readily recognised on MRI than on CT, supporting the role of MRI in cases of traumatic brain injury.

Brain damage associated with apraxia of speech: evidence from case studies.

The site of crucial damage that causes acquired apraxia of speech (AOS) has been debated in the literature. This study presents five in-depth cases that offer insight into the role of brain areas involved in AOS. Four of the examined participants had a primary impairment of AOS either with (n = 2) or without concomitant mild aphasia (n = 2). The fifth participant presented with a lesion relatively isolated to the left anterior insula (AIns-L), damage that is rarely reported in the literature, but without AOS. Taken together, these cases challenge the role of the AIns-L and implicate the left motor regions in AOS.

[Comparative Analysis of the Brain Activity during Verbal and Spatial Thinking in Healthy Subjects and Patients with Speech Disorders].

We analyzed the specific brain activity, measured by fMRI in spatial and verbal tasks, in 15 healthy sub- jects and in 9 patients with dysarthria or mild sensorimotor aphasia. In healthy participants, verbal thinking was characterized by activation in Brodmann area 19 and Broca area while specific activation for spatial thinking was observed in bilateral temporal-occipital-parietal areas, left insula, left visual fields 17 and 18. In patients with impaired speech, this distribution of networks specific to a particular type of task underwent significant changes with deactivation of the brain areas, as compared to healthy subjects. Despite the absence of clinical manifestations of cognitive impairment, the average time .to solve verbal tasks was significantly higher, and the percentage of correct answers was less in patients as compared to these values for a group of healthy subjects.

Clinical and imaging characterization of progressive spastic dysarthria.

BACKGROUND AND PURPOSE: To describe speech, neurological and imaging characteristics of a series of patients presenting with progressive spastic dysarthria as the first and predominant sign of a presumed neurodegenerative disease. METHODS: Participants were 25 patients with spastic dysarthria as the only or predominant speech disorder. Clinical features, pattern of MRI volume loss on voxel-based morphometry and pattern of hypometabolism on F18-fluorodeoxyglucose positron emission tomography (FDG-PET) scan are described. RESULTS: All patients demonstrated speech characteristics consistent with spastic dysarthria, including strained voice quality, slow speaking rate, monopitch and monoloudness, and slow and regular speech alternating motion rates. Eight patients did not have additional neurological findings on examination. Pseudobulbar affect, upper motor neuron pattern limb weakness, spasticity, Hoffman sign and positive Babinski reflexes were noted in some of the remaining patients. Twenty-three patients had electromyographic assessment and none had diffuse motor neuron disease or met El Escorial criteria for amyotrophic lateral sclerosis. Voxel-based morphometry revealed striking bilateral white matter volume loss affecting the motor cortex (BA 4), including the frontoparietal operculum (BA 43) with extension into the middle cerebral peduncle. FDG-PET showed subtle hypometabolism affecting the premotor and motor cortices in some patients, particularly in those who had a disease duration longer than 2 years. CONCLUSIONS: A neurodegenerative disorder that begins focally with spastic dysarthria due to involvement of the motor and premotor cortex and descending corticospinal and corticobulbar pathways is characterized. The descriptive label 'progressive spastic dysarthria' to best capture the dominant presenting feature of the syndrome is proposed.

Friedreich ataxia: dysarthria profile and clinical data.

Friedreich ataxia (FRDA) is the most frequent recessive ataxia in the Western world. Dysarthria is a cardinal feature of FRDA, often leading to severe impairments in daily functioning, but its exact characteristics are only poorly understood so far. We performed a comprehensive evaluation of dysarthria severity and the profile of speech motor deficits in 20 patients with a genetic diagnosis of FRDA based on a carefully selected battery of speaking tasks and two widely used paraspeech tasks, i.e., oral diadochokinesis and sustained vowel productions. Perceptual ratings of the speech samples identified respiration, voice quality, voice instability, articulation, and tempo as the most affected speech dimensions. Whereas vocal instability predicted ataxia severity, tempo turned out as a significant correlate of disease duration. Furthermore, articulation predicted the overall intelligibility score as determined by a systematic speech pathology assessment tool. In contrast, neurologists' ratings of intelligibility--a component of the "Scale for the Assessment and Rating of Ataxia"--were found to be related to perceived speech tempo. Obviously, clinicians are more sensitive to slowness of speech than to any other feature of spoken language during dysarthria evaluation. Our results suggest that different components of speech production and trunk/limb motor functions are differentially susceptible to FRDA pathology. Furthermore, evidence emerged that paraspeech tasks do not allow for an adequate scaling of speech deficits in FRDA.

Acquired epileptiform opercular syndrome: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings and efficacy of levetiracetam therapy.

We report a five-year-old girl presenting with dysphagia, dysarthria, drooling, and generalized tonic convulsions in whom the final diagnosis was acquired epileptiform opercular syndrome. Levetiracetam monotherapy at a dosage of 40 mg/kg/day improved the clinical findings, and seizures were controlled at the end of the first month of treatment. Six months after the initial diagnosis, she presented with speech deterioration and dysarthria. At this time, although sleep and awake electroencephalography (EEG) were normal, FDG-PET showed hypometabolic and hypermetabolic regions in the anterior/inferior and anterior regions of the right frontal lobe, respectively. By increasing before levetiracetam dosage to 50 mg/kg/day, the clinical findings resolved and the patient is still seizure free. Acquired epileptiform opercular syndrome is a rare epileptic disorder in which the seizures are resistant to conventional antiepileptic drugs. Levetiracetam may be an effective antiepileptic drug in controlling seizures and other clinical findings in acquired opercular epileptiform syndrome. Hypometabolic and hypermetabolic regions in FDG-PET study may be due to ongoing seizure activity or impaired glucose metabolism in this disorder.

A speech expression disorder in patients with severe diffuse brain injury who emerged from a vegetative or minimally conscious state.

OBJECTIVE: The purpose of this study was to highlight a speech expression disorder considered as a mixed speech apraxia (SA) and dysarthria syndrome in patients with chronic severe diffuse brain injury (DBI) and to determine its correlation with anatomical localizations of brain lesions using neuroimaging. METHODS: Among 140 patients with chronic severe DBI, eight showed this type of speech disorder. MRI (five patients) and FDG-PET (six patients) procedures were performed. RESULTS: Affected patients could comprehend verbally, read words silently and express words using a word board. Compared with SA, the disorder is characterized by similarities in regards to reduced phonation and marked facio-oral apraxia, but by distinct differences in terms of an accompanying dysphagia and pyramidal/extra-pyramidal symptoms that are similar to symptoms associated with dysarthria due to pseudobulbar palsy. Diffuse regions of the white matter including the left arcuate fasciculus (AF) were significantly decreased in fractional anisotropy value. However, there was no significant cortical metabolic damage in FDG-PET. CONCLUSIONS: The observed speech disorder in these patients is a characteristic entity related to dysfunction of speech expression and may be attributable to damage of not only the AF but also a number of fibres that are related to dysarthria, cognitive and emotional impairments and pyramidal/extra-pyramidal symptoms.

Anti-IgLON5 disease with distinctive brain MRI findings responding to immunotherapy: A case report.

RATIONALE: Anti-IgLON5 disease was first described as a progressive antibody-associated encephalopathy, with multiple non-specific clinical symptoms including sleep dysfunction, bulbar symptoms, progressive supranuclear palsy-like syndrome, cognitive impairment, and a variety of movement disorders. This newly discovered disease presents with unremarkable or unspecific brain magnetic resonance imagings (MRI), and have poor responsiveness to immunotherapy. PATIENT CONCERNS: In this case, a 37-year-old man presented with 4-day history of gait instability, dysarthria, and oculomotor abnormalities. The initial neurologic examination revealed mild unsteady gait, subtle dysarthria, and left abducent paralysis. DIAGNOSIS: The patient was diagnosed with anti-IgLON5 disease, based on clinical features and positive anti-IgLON5 antibodies in serum. INTERVENTIONS: Initially, the patient was treated with high dosages of methylprednisolone and immunoglobulins.Outcomes: The symptoms of patient rapidly improved after high-dose intravenous methylprednisolone and immunoglobulins. CONCLUSIONS: In this paper, we report a new case of anti-IgLON5 disease with major symptoms of gait instability, dysarthria, and oculomotor abnormalities, with distinctive brain MRI findings, and responsive to immunotherapy.

Paroxysmal dysarthria-ataxia syndrome: Literature review on MRI findings and report of a peculiar case with clinically isolated syndrome coexisting with anti-N-methyl-d-aspartate receptor antibodies.

Paroxysmal dysarthria and ataxia (PDA) syndrome constitutes a rare neurological disorder, and is generally reported in cases of multiple sclerosis (MS) involving the midbrain. We present an illustrative case of 32-year-old female who developed clinically isolated syndrome manifested paroxysmal dysarthria, ataxia, ptosis and diplopia, coexisting with anti-N-methyl-d-aspartate receptor antibodies. We review the literature and identify 23 other cases with brain MRI examinations to summarize the lesion locations and clinical characteristics of PDA syndrome, and ultimately provide a new framework for understanding this rare condition. The current case expands the spectrum of symptoms in PDA syndrome, which was including but not limited to dysarthria and ataxia. Caudal paramedian midbrain lesions involving decussation of the superior cerebellar peduncles appear to be critical for PDA syndrome.

Bilateral pontine infarction with basilar artery fenestration: A case report.

RATIONALE: Basilar artery (BA) fenestration is a congenital anomaly with duplicated BA, which can cause ischemic stroke. However, the stroke mechanism is not clearly verified in patients with BA fenestration. PATIENT CONCERNS: Here, we report a case of 64-year-old man with well-controlled hypertension admitted with dysarthria, only. DIAGNOSES: Diffusion weighted image showed a bilateral symmetric pontine infarction sparing the midline. BA fenestration was observed from magnetic resonance angiography. INTERVENTION: High-resolution magnetic resonance image (MRI) and 4D flow MRI was performed to verify the mechanism of stroke associated with BA fenestration. OUTCOMES: No plaque was observed at the area of BA fenestration from high-resolution MRI. 4D flow MRI showed bifurcated flow with high flow velocity and low shear stress at the area of BA fenestration. LESSONS: A turbulent flow with high flow velocity and low shear stress at the BA fenestration area may have influenced the flow through the bilateral perforating arteries resulting in a bilateral symmetric pontine infarction with sparing the midline where the septa of BA is located. 4D flow dynamic studies may be beneficial for verifying the mechanism of stroke.

Brain morphological changes in hypokinetic dysarthria of Parkinson's disease and use of machine learning to predict severity.

BACKGROUND: Up to 90% of patients with Parkinson's disease (PD) eventually develop the speech and voice disorder referred to as hypokinetic dysarthria (HD). However, the brain morphological changes associated with HD have not been investigated. Moreover, no reliable model for predicting the severity of HD based on neuroimaging has yet been developed. METHODS: A total of 134 PD patients were included in this study and divided into a training set and a test set. All participants underwent a structural magnetic resonance imaging (MRI) scan and neuropsychological evaluation. Individual cortical thickness, subcortical structure, and white matter volume were extracted, and their association with HD severity was analyzed. After feature selection, a machine-learning model was established using a support vector machine in the training set. The severity of HD was then predicted in the test set. RESULTS: Atrophy of the right precentral cortex and the right fusiform gyrus was significantly associated with HD. No association was found between HD and volume of white matter or subcortical structures. Favorable and optimal performance of machine learning on HD severity prediction was achieved using feature selection, giving a correlation coefficient (r) of .7516 and a coefficient of determination (R2 ) of .5649 (P < .001). CONCLUSION: The brain morphological changes were associated with HD. Excellent prediction of the severity of HD was achieved using machine learning based on neuroimaging.

Right fronto-parietal white matter disruption contributes to speech impairments in amyotrophic lateral sclerosis.

INTRODUCTION: Non-linguistic properties of speech are widely heterogeneous and require complex neurological integration. The association between white matter integrity and the severity of dysarthria was investigated in a group of patients diagnosed with amyotrophic lateral sclerosis (ALS). METHODS: Thirty-six patients diagnosed with amyotrophic lateral sclerosis completed a magnetic resonance imaging protocol inclusive of diffusion-weighted images. A clinical assessment of pneumo-phono-articulatory abilities was conducted for each patient, and a composite score of residual speech capacity was calculated. Tract-Based Spatial Statistics was carried out to model the potential association between residual speech capacity and microstructural properties of white matter (fractional anisotropy, mean and radial diffusivity). RESULTS: A significant negative association was found between residual speech capacity and mean diffusivity in a large white matter cluster located in frontal, parietal and right temporal regions. These subcortical areas were characterised by pathological microstructural disruption, as revealed by post hoc analyses. CONCLUSIONS: Non-linguistic aspects of speech are associated with microstructural integrity of frontal, parietal and right temporal white matter in amyotrophic lateral sclerosis. Such mapping is consistent with the centres responsible of volitional control of speech and sensory feedback during non-linguistic speech production.

Brain volumetric correlates of dysarthria in multiple sclerosis.

Although dysarthria is a common pattern in multiple sclerosis (MS), the contribution of specific brain areas to key factors of dysarthria remains unknown. Speech data were acquired from 123 MS patients with Expanded Disability Status Scale (EDSS) ranging from 1 to 6.5 and 60 matched healthy controls. Results of computerized acoustic analyses of subtests on spastic and ataxic aspects of dysarthria were correlated with MRI-based brain volume measurements. Slow articulation rate during reading was associated with bilateral white and grey matter loss whereas reduced maximum speed during oral diadochokinesis was related to greater cerebellar involvement. Articulation rate showed similar correlation to whole brain atrophy (r = 0.46, p < 0.001) as the standard clinical scales such as EDSS (r = -0.45, p < 0.001). Our results support the critical role of the pyramidal tract and cerebellum in the modification of motor speech timing in MS.

Non-invasive stimulation of the auditory feedback area for improved articulation in Parkinson's disease.

INTRODUCTION: Hypokinetic dysarthria (HD) is a common symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated acute effects of repetitive transcranial magnetic stimulation (rTMS) of the motor and auditory feedback area on HD in PD using acoustic analysis of speech. METHODS: We used 10 Hz and 1 Hz stimulation protocols and applied rTMS over the left orofacial primary motor area, the right superior temporal gyrus (STG), and over the vertex (a control stimulation site) in 16 PD patients with HD. A cross-over design was used. Stimulation sites and protocols were randomised across subjects and sessions. Acoustic analysis of a sentence reading task performed inside the MR scanner was used to evaluate rTMS-induced effects on motor speech. Acute fMRI changes due to rTMS were also analysed. RESULTS: The 1 Hz STG stimulation produced significant increases of the relative standard deviation of the 2nd formant (p = 0.019), i.e. an acoustic parameter describing the tongue and jaw movements. The effects were superior to the control site stimulation and were accompanied by increased resting state functional connectivity between the stimulated region and the right parahippocampal gyrus. The rTMS-induced acoustic changes were correlated with the reading task-related BOLD signal increases of the stimulated area (R = 0.654, p = 0.029). CONCLUSION: Our results demonstrate for the first time that low-frequency stimulation of the temporal auditory feedback area may improve articulation in PD and enhance functional connectivity between the STG and the cortical region involved in an overt speech control.

Dysarthria in pallidal Deep Brain Stimulation in dystonia depends on the posterior location of active electrode contacts: a pilot study.

BACKGROUND: Pallidal Deep Brain Stimulation (GPi-DBS) is an efficient treatment for primary dystonia. We investigated stimulation-induced dysarthria, which is the most frequent side-effect of GPi-DBS. METHODS: Speech was recorded while reading a standard text, and performing rapid syllable repetitions ON and OFF DBS in ten dystonia patients (6 men; 3 cervical, 4 segmental, 3 generalized, unselected for DBS-related speech impairments). Speech and articulation rate, pauses, and syllable repetition rates were extracted via acoustic analysis. Locations of active stimulation contacts and volumes of tissue activated (VTA) were calculated. RESULTS: The number of pauses increased significantly ON vs. OFF stimulation (Wilcoxon test, p < 0.05). More posteriorly localized active contacts were associated with slower syllable repetition (Pearson correlation, p < 0.05). VTA size did not correlate with any measure of dysarthria. CONCLUSION: Using quantitative acoustic signal analysis, this study demonstrates that GPi-DBS alters motor aspects of speech. Both inadvertent stimulation of parts of the internal capsule, or interference with GPi function and outflow are possible causes. Understanding causes of GPi-DBS-induced speech changes can improve DBS programming.