Levodopa may modulate specific speech impairment in Parkinson's disease: an fMRI study.

Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.

Automated speech analysis in early untreated Parkinson's disease: Relation to gender and dopaminergic transporter imaging.

BACKGROUND: The mechanisms underlying speech abnormalities in Parkinson's disease (PD) remain poorly understood, with most of the available evidence based on male patients. This study aimed to estimate the occurrence and characteristics of speech disorder in early, drug-naive PD patients with relation to gender and dopamine transporter imaging. METHODS: Speech samples from 60 male and 40 female de novo PD patients as well as 60 male and 40 female age-matched healthy controls were analyzed. Quantitative acoustic vocal assessment of 10 distinct speech dimensions related to phonation, articulation, prosody, and speech timing was performed. All patients were evaluated using [123]I-2b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single-photon emission computed tomography and Montreal Cognitive Assessment. RESULTS: The prevalence of speech abnormalities in the de novo PD cohort was 56% for male and 65% for female patients, mainly manifested with monopitch, monoloudness, and articulatory decay. Automated speech analysis enabled discrimination between PD and controls with an area under the curve of 0.86 in men and 0.93 in women. No gender-specific speech dysfunction in de novo PD was found. Regardless of disease status, females generally showed better performance in voice quality, consonant articulation, and pauses production than males, who were better only in loudness variability. The extent of monopitch was correlated to nigro-putaminal dopaminergic loss in men (r = 0.39, p = 0.003) and the severity of imprecise consonants was related to cognitive deficits in women (r = -0.44, p = 0.005). CONCLUSIONS: Speech abnormalities represent a frequent and early marker of motor abnormalities in PD. Despite some gender differences, our findings demonstrate that speech difficulties are associated with nigro-putaminal dopaminergic deficits.

Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities.

BACKGROUND: The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early-stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI). METHODS: The sample age range was 6-16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1-3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status. RESULTS: Cerebellar gray matter volume was significantly smaller in pCKD, t(38) = -2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38) = 2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14) = 2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment. CONCLUSIONS: This study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD. IMPACT: The impact of pediatric chronic kidney disease (CKD) on the brain remains poorly defined, with no data linking brain morphometry and observed cognitive deficits noted in this population. We explored the relationship between brain morphometry (using structural magnetic resonance imaging), cognition, and markers of CKD. Cerebellar and cerebral gray matter volumes are different in early CKD. Volumetric decreases in cerebellar gray matter are predicted by lower eGFR, suggesting a link between disease and brain morphometry. Reduced cerebellar gray matter predicted lower verbal fluency for those with pCKD. Enlarged cerebral gray matter in the pCKD sample predicted lower mathematics performance.

A Brain Marker for Developmental Speech Disorders.

OBJECTIVE: To characterize the organization of speech- and language-related white matter tracts in children with developmental speech and/or language disorders. STUDY DESIGN: We collected magnetic resonance diffusion-weighted imaging data from 41 children, ages 9-11 years, with developmental speech and/or language disorders, and compared them with 45 typically developing controls with the same age range. We used probabilistic tractography of diffusion-weighted imaging to map language (3 segments of arcuate fasciculus, extreme capsule system) and speech motor (corticobulbar) tracts bilaterally. The corticospinal and callosal tracts were used as control regions. We compared the mean fractional anisotropy and diffusivity values between atypical and control groups, covarying for nonverbal IQ. We then examined differences between atypical subgroups: developmental speech disorder (DSD), developmental language disorder, and co-occurring developmental speech and language disorder. RESULTS: Fractional anisotropy in the left corticobulbar tract was lower in the DSD than in the control group. Radial and mean diffusivity were higher in the DSD than the developmental language disorder, co-occurring developmental speech and language disorder, or control groups. There were no group differences for any metrics in the language or control tracts. CONCLUSIONS: Atypical development of the left corticobulbar tract may be a neural marker for DSD. This finding is in line with reports of speech disorder after left corticobulbar damage in children and adults with brain injury. By contrast, we found no association between diffusion metrics in language-related tracts in developmental language disorder, and changes for language disorders are likely more complex.

Clinical and imaging progression over 10 years in a patient with primary progressive apraxia of speech and autopsy-confirmed corticobasal degeneration.

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative disorder in which AOS is the sole presenting complaint. We report clinical and neuroimaging data spanning 10 years from disease onset-to-death in a 49 year-old male PPAOS patient, DY, who died with corticobasal degeneration. He presented with AOS with normal neuroimaging. Abnormalities in the caudate nucleus, supplementary motor area, cingulate, insula, and Broca's area were observed after five years, with involvement of motor cortex and development of agrammatism, Parkinsonism, and dysarthria three years later. Cognitive impairment and temporoparietal atrophy were late features. This data provides important insight into disease progression of corticobasal degeneration when presenting as PPAOS.

White matter correlates of the disorganized speech dimension in schizophrenia.

Disorganized speech is related to functional abnormalities in schizophrenia. To test the association between formal thought disorders (FTDs) and white matter microstructure, we applied a behavioral rating and diffusion tensor imaging in 61 patients with schizophrenia spectrum disorders. The Bern Psychopathology Scale was used to rate the dimension of language abnormalities ranging from negative FTDs, basically unaltered speech, to positive FTDs. Tract-based spatial statistics indicated increased fractional anisotropy in left hemispheric pathways of the language system in patients with negative FTDs. Thus, altered white matter properties in relevant fiber tracts may represent vulnerability to specific formal thought disorders.

Supplementary motor area syndrome after surgery for parasagittal meningiomas.

BACKGROUND: Resection within the supplementary motor area (SMA) may be accompanied by dramatic motor deficits and speech arrest when the dominant hemisphere is involved, termed the SMA syndrome. Typically, the muscle tone of the paralyzed extremities is preserved, and in most cases, a complete or near complete recovery is seen within a few months. The SMA syndrome has not been recognized for extra-axial tumor surgery in approximation of the SMA. METHODS: We observed the SMA syndrome in a patient operated for a parasagittal meningioma in the posterior frontal region, and this observation intrigued us to prospectively collect similar cases. RESULTS: In the period from January 2010 to December 2015, we observed five patients who developed a partial SMA syndrome after surgery for frontal parasagittal meningiomas. The muscle tone was preserved in the affected extremities. All patients experienced improvement in motor function within a few days, and on follow-up, three out of five patients had recovered completely. Three of the patients had meningioma WHO grade II. CONCLUSIONS: Surgically induced SMA syndrome can easily be confused with pyramidal weakness. This series of cases demonstrate that the syndrome may also develop after removal of extra-axial tumors and is probably underdiagnosed and underreported. The good functional prognosis is helpful in the preoperative counseling and follow-up of these patients.

The Posterior Fossa and Foreign Accent Syndrome: Report of Two New Cases and Review of the Literature.

Foreign accent syndrome is a rare motor speech disorder that causes patients to speak their language with a non-native accent. In the neurogenic condition, the disorder develops after lesions in the language dominant hemisphere, often affecting Broca's area, the insula, the supplementary motor area and the primary motor cortex. Here, we present two new cases of FAS after posterior fossa lesions. The first case is a 44-year-old, right-handed, Dutch-speaking man who suffered motor speech disturbances and a left hemiplegia after a pontine infarction. Quantified SPECT showed a bilateral hypoperfusion in the inferior lateral prefrontal and medial inferior frontal regions as well as a significant left cerebellar hypoperfusion. Further clinical investigations led to an additional diagnosis of brainstem cognitive affective syndrome which closely relates to Schmahmann's syndrome. The second patient was a 72-year-old right-handed polyglot English man who suffered a stroke in the vascular territory of the left posterior inferior cerebellar artery (PICA) and developed a foreign accent in his mother tongue (English) and in a later learnt language (Dutch). In this paper, we discuss how the occurrence of this peculiar motor speech disorder can be related to a lesion affecting the posterior fossa structures.

Psychotic-Like Speech in Frontotemporal Dementia.

Behavioral variant frontotemporal dementia (bvFTD) may result in psychotic-like speech without other psychotic features. The authors identified a bvFTD subgroup with pressure of speech, tangentiality, derailment, clanging/rhyming, and punning associated with the right anterior temporal atrophy and sparing of the left frontal lobe.

Neuroanatomical Correlates of Hypophonia in Subcortical Vascular Cognitive Impairment.

BACKGROUND/AIMS: Early detection and intervention may alter the disease course of subcortical vascular cognitive impairment (SVCI). Patients with SVCI have white matter ischemia that disrupts connections between the cortex and subcortical gray matter and therefore manifest various symptoms such as motor disturbances and behavioral/cognitive dysfunction. Reduced vocal loudness, or hypophonia, is one of the common motor symptoms of SVCI, but few studies have systematically investigated it in this patient population. The main purpose of this investigation was to identify neural pathways underlying hypophonia in patients with SVCI. METHODS: Eighty-eight patients with SVCI and 21 normal controls performed phonation tasks. Diffusion tensor imaging data from 73 patients were utilized to measure white matter changes associated with hypophonia. RESULTS: Correlational analyses between white matter fractional anisotropy values and the decibel level of the "sustained phonation" task identified the left midbrain cerebral peduncle (corticobulbar tract), external capsule, corona radiata/internal capsule, and bilateral frontal white matter as possible neural correlates for hypophonia. CONCLUSION: Our results support the notion that hypophonia in SVCI patients might be caused by the impairment of the pyramidal and extrapyramidal systems. This study provides a unique contribution towards understanding the neuropathology of hypophonic features in this population.

[Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts]. / Khirurgicheskoe lechenie opukholei funktsional'no znachimykh zon golovnogo mozga s primeneniem metoda neirofiziologicheskogo kartirovaniya rechevykh, motornykh zon i provodyashchikh putei.

AIM: To evaluate the efficacy of intraoperative neurophysiological mapping in removing eloquent brain area tumors (EBATs). MATERIAL AND METHODS: Sixty five EBAT patients underwent surgical treatment using intraoperative neurophysiological mapping at the Pirogov National Medical and Surgical Center in the period from 2014 to 2015. On primary neurological examination, 46 (71%) patients were detected with motor deficits of varying severity. Speech disorders were diagnosed in 17 (26%) patients. Sixteen patients with concomitant or isolated lesions of the speech centers underwent awake surgery using the asleep-awake-asleep protocol. Standard neurophysiological monitoring included transcranial stimulation as well as motor and, if necessary, speech mapping. The motor and speech areas were mapped with allowance for the preoperative planning data (obtained with a navigation station) synchronized with functional MRI. In this case, a broader representation of the motor and speech centers was revealed in 12 (19%) patients. During speech mapping, no speech disorders were detected in 7 patients; in 9 patients, stimulation of the cerebral cortex in the intended surgical area induced motor (3 patients), sensory (4), and amnesic (2) aphasia. In the total group, we identified 11 patients in whom the tumor was located near the internal capsule. Upon mapping of the conduction tracts in the internal capsule area, the stimulus strength during tumor resection was gradually decreased from 10 mA to 5 mA. Tumor resection was stopped when responses retained at a stimulus strength of 5 mA, which, when compared to the navigation data, corresponded to a distance of about 5 mm to the internal capsule. Completeness of tumor resection was evaluated (contrast-enhanced MRI) in all patients on the first postoperative day. RESULTS: According to the control MRI data, the tumor was resected totally in 60% of patients, subtotally in 24% of patients, and partially in 16% of patients. In the early postoperative period, the development or aggravation of a motor neurological deficit was detected in 18 patients: worsening of paresis was observed in 11 patients, and worsening of speech disorders occurred in 7 patients. After 4 months, motor and speech disorders regressed in 10 patients. Therefore, a persistent neurological deficit developed after surgery in 8 (12%) patients (motor deficit in 5 cases; speech deficit in 3 cases). CONCLUSION: Resection of eloquent brain area tumors using intraoperative neurophysiological monitoring enables complete resection of the tumor at a low risk of persistent neurological deficits, which ultimately improves the patient's life prognosis.

[Dynamics of functional MRI and speech function in patients after resection of frontal and temporal lobe tumors]. / Dinamika funktsional'noi MRT i rechevoi funktsii u bol'nykh posle udaleniia vnutrimozgovykh opukholei lobnoi i visochnoi dolei mozga.

RATIONALE: There are no studies on application of functional MRI (fMRI) for long-term monitoring of the condition of patients after resection of frontal and temporal lobe tumors. PURPOSE: The study purpose was to correlate, using fMRI, reorganization of the speech system and dynamics of speech disorders in patients with left hemisphere gliomas before surgery and in the early and late postoperative periods. MATERIAL AND METHODS: A total of 20 patients with left hemisphere gliomas were dynamically monitored using fMRI and comprehensive neuropsychological testing. The tumor was located in the frontal lobe in 12 patients and in the temporal lobe in 8 patients. Fifteen patients underwent primary surgery; 5 patients had repeated surgery. Sixteen patients had WHO Grade II and Grade III gliomas; the others had WHO Grade IV gliomas. Nineteen patients were examined preoperatively; 20 patients were examined at different times after surgery. Speech functions were assessed by a Luria's test; the dominant hand was determined using the Annette questionnaire; a family history of left-handedness was investigated. Functional MRI was performed on an HDtx 3.0 T scanner using BrainWavePA 2.0, Z software for fMRI data processing program for all calculations >7, p<0.001. RESULTS: In patients with extensive tumors and recurrent tumors, activation of right-sided homologues of the speech areas cold be detected even before surgery; but in most patients, the activation was detected 3 months or more after surgery. Therefore, reorganization of the speech system took time. Activation of right-sided homologues of the speech areas remained in all patients for up to a year. Simultaneous activation of right-sided homologues of both speech areas, the Broca's and Wernicke's areas, was detected more often in patients with frontal lobe tumors than in those with temporal lobe tumors. No additional activation foci in the left hemisphere were found at the thresholds used to process fMRI data. Recovery of the speech function, to a certain degree, occurred in all patients, but no clear correlation with fMRI data was found. CONCLUSION: Complex fMRI and neuropsychological studies in 20 patients after resection of frontal and temporal lobe tumors revealed individual features of speech system reorganization within one year follow-up. Probably, activation of right-sided homologues of the speech areas in the presence of left hemisphere tumors depends not only on the severity of speech disorder but also reflects individual involvement of the right hemisphere in enabling speech function. This is confirmed by right-sided activation, according to the fMRI data, in right-sided patients without aphasia and, conversely, the lack of activation of right-sided homologues of the speech areas in several patients with severe postoperative speech disorders during the entire follow-up period.

Brain basis of childhood speech and language disorders: are we closer to clinically meaningful MRI markers?

PURPOSE OF REVIEW: Developmental speech and language disorders are common, seen in one in 20 preschool children, in the absence of frank neurological deficits or intellectual impairment. They are a key reason parents seek help from paediatricians. Complex neurogenetic and environmental contributions underpin the disorders, yet few specific causes are known. With the advent of quantitative brain imaging, a growing number of studies have investigated neural contributions. Here, we discuss current MRI approaches and recent findings (January 2014-June 2016) in the field. RECENT FINDINGS: Five relevant studies were identified (n = 3 - speech disorder and n = 2 - language disorder). Significant variability in MRI approaches and heterogeneity of participant phenotypes was seen. Children with speech disorder had structural and functional anomalies in the left supramarginal gyrus and functional anomalies in the posterior cerebellum bilaterally - regions critical for sensory-motor integration or feedback. Children with language disorder showed increased mean and radial diffusivity of the left arcuate fasciculus, although a widespread cortical and subcortical network of regions was implicated. SUMMARY: Limited evidence exists for specific regional brain anomalies in this population. MRI prognostic markers of speech and language ability are not currently available at an individual level. Further work is required to disentangle neurobiological contributions to speech and language disorders for affected children.

Radiology case of the month. Progressive slurring of speech and difficulty reading in a 62-year-old male. Final diagnosis: Metastatic small cell cancer of the prostate gland.

A 62-year-old male with controlled hypertension, coronary artery disease, and borderline diabetes presented to the emergency room after experiencing a gradual one-month progression of slurring of speech and difficulty reading. The patient maintained his vital signs throughout his ambulance ride to the hospital and was clinically stable at time of arrival to the emergency department.

Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech.

Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [(18)F]-fluorodeoxyglucose and [(11)C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49-82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy and increased mean diffusivity of the superior longitudinal fasciculus, particularly the premotor components. Statistical parametric mapping of the [(18)F]-fluorodeoxyglucose positron emission tomography scans revealed focal hypometabolism of superior lateral premotor cortex and supplementary motor area, although there was some variability across subjects noted with CortexID analysis. [(11)C]-Pittsburg compound B positron emission tomography binding was increased in only one of the 12 subjects, although it was unclear whether the increase was actually related to the primary progressive apraxia of speech. A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia.

Postnatal neuro-development of fetuses with absent end-diastolic flow in the umbilical artery and/or fetal descending aorta.

OBJECTIVE: To determine whether absence of end-diastolic flow in the umbilical artery and/or fetal aorta impacts postnatal neuro-development in preterm-born children. METHODS: The study group, consisting of 43 fetuses with absent end-diastolic flow in the umbilical artery and/or fetal aorta, was compared with a control group, consisting of 30 fetuses, matching for gestational age but with normal doppler-flow results. The children's neuro-developmental status was assessed using the 'Munich functional developmental diagnostics' (MFDD), between the 2nd and 3rd year of life. RESULTS: Gestational age at birth was 33 + 6 weeks in the study group and 34 + 4 weeks in the control group. A brain-sparing effect was observed in 37.3% of fetuses in the study group compared with 10.0% in the control group (p = 0.014). For all seven MFDD domains, the number of children with deficiencies was higher in the study group. For the domains perception, active speech and comprehension this effect was statistically significant (p < 0.05). Overall, 30.2% of children in the study group and 16.7% of the control group had pathologic test results (p < 0.013). CONCLUSION: Pathological doppler-flow in the umbilical artery and/or fetal descending aorta in preterm born children is associated with neuro-developmental deficiencies. Intensive pediatric care is recommended to mitigate these deficiencies during early childhood.