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.

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.

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.

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.

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.

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.

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.

Neural Correlates of Hypokinetic Dysarthria and Mechanisms of Effective Voice Treatment in Parkinson Disease.

BACKGROUND: Hypokinetic dysarthria is highly prevalent in idiopathic Parkinson disease (PD), and effectiveness of high-intensity voice treatment is well established. However, the neural correlates remain largely unknown. OBJECTIVE: We aimed to specify cerebral pathophysiology of hypokinetic dysarthria and treatment-induced changes using functional magnetic resonance imaging (fMRI). METHODS: We used fMRI to investigate healthy controls (HCs) and patients with idiopathic PD-associated dysarthria before and after treatment according to the Lee Silverman Voice Treatment LOUD (LSVT). During fMRI, participants covertly read sentences with normal (eg, conversation in a quiet room) or high (eg, shouting on a windy beach) intensity. In addition, we tested LSVT effects on intelligibility and different speech features (intensity, pitch, articulation). RESULTS: LSVT effectively improved intelligibility, articulation, and pitch in patients. Covert high-intensity speech compared with covert normal-intensity speech led to increased activation of mainly secondary motor areas and bilateral superior and medial temporal regions. Prior to LSVT, patients showed less activity in several speech-associated areas compared with HCs. As a neural correlate of effective LSVT, increased right-sided superior temporal activity correlated with improved intelligibility. CONCLUSION: This is the first brain imaging study using a covert speech paradigm in PD, which revealed cortical hypoactivation as correlate of hypokinetic dysarthria. Furthermore, cortical correlates of effective LSVT treatment colocalized with the neuronal network, showing increased activation during high- versus normal-intensity speech generation.