[Possibilities of neurotrophic therapy for delayed speech development]. / Vozmozhnosti neirotroficheskoi terapii zaderzhki rechevogo razvitiya.

The article provides an analysis of the possibility of neurotrophic therapy of delayed speech development (DSD) in 266 children who underwent dynamic clinical, laboratory, functional and neuropsychological examinations and received neurotrophic therapy. This study confirmed the effectiveness of neurotrophic therapy in the treatment of as isolated speech disorder (ISD) as well speech disorder in the structure of the general psychomotor developmental delay (PDD). The lack of effect in the use of neuroprotective therapy in every sixth child of the latter group can be a marker for the individualization of the treatment of each individual with an emphasis on non-drug rehabilitation methods. The use of cortexin in monotherapy in the treatment of delayed speech development is justified not only by its effectiveness in improving speech development and good tolerance, but also in connection with an improvement in behavior in children of the studied groups, which is possibly associated with a positive effect on mental activity in general, and on self-control function in particular.

Does Pregnenolone Adjunct to Risperidone Ameliorate Irritable Behavior in Adolescents With Autism Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial?

OBJECTIVES: Pregnenolone is a neurosteroid with modulatory effects on γ-aminobutyric acid neurotransmission. Here, we aimed to evaluate the effectiveness and safety of pregnenolone add-on to risperidone in adolescents with autism spectrum disorders (ASD). METHODS: Sixty-four ASD patients were randomly allocated to receive either pregnenolone (n = 32) or matching placebo (n = 32) in addition to risperidone. The Aberrant Behavior Checklist-Community Edition scale was used to evaluate the behavioral status of patients at baseline, week 5, and the trial end point. The change in score of irritability subscale was the primary outcome. Frequency of adverse effects due to trial medications was compared between the treatment groups. RESULTS: Fifty-nine patients completed the trial (30 in pregnenolone and 29 in the placebo arm). Baseline characteristics of both treatment groups were similar (P > 0.05). Repeated measures analysis was suggestive of greater exhibited improvement for the pregnenolone group on irritability, stereotypy, and hyperactivity subscales of the Aberrant Behavior Checklist-Community Edition over the trial period (F = 3.84, df = 1.96, P = 0.025; F = 4.29, df = 1.39, P = 0.029; F = 6.55, df = 1.67, P = 0.004, respectively). Nonetheless, the alterations in lethargy and inappropriate speech domains scores were similar for both arms (F = 0.93, df = 1.49, P = 0.375; F = 1.10, df = 1.60, P = 0.325, respectively). There was no significant difference in frequency as well as severity of adverse effects between the 2 groups. CONCLUSIONS: Pregnenolone adjunct to risperidone could attenuate core features associated with ASD.

Serum and CSF Anti-NMDAR Antibody Testing in Psychiatry.

OBJECTIVE: The authors examined and compared the clinical presentation of CSF positive and negative N-methyl-d-aspartate receptor (NMDAR) antibody. METHODS: The investigators performed a retrospective chart review of NMDAR-antibody-positive cases (serum or CSF) involving patients presenting to psychiatric services from 2010 to 2018 in Queensland, Australia. Presentation, progress, investigations, and efficacy of treatment are detailed. RESULTS: There were 24 serum or CSF NMDAR-antibody-positive cases and three equivocal serum results. High rates of prodromal cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity were observed in the 16 CSF NMDAR-antibody-positive case patients and two CSF NMDAR-antibody-negative case patients, all evident before neurological deterioration with seizures, movement disorder, and autonomic disturbance occurring in the weeks following admission. The majority of these patients (N=17) were treated successfully with immunomodulatory therapy. The nine remaining patients, who were CSF NMDAR antibody negative or equivocal, did not demonstrate any of these features and improved with psychiatric care alone. CONCLUSIONS: These findings suggest that traditional psychiatric care may be appropriate for patients with isolated psychiatric symptoms who have positive serum NMDAR testing when CSF is negative and there are no key clinical features such as cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity. However, if these key features are present, a trial of immunomodulatory treatment should be considered with repeated examination of CSF for neuronal antibodies.

Velopharyngeal Dystonia: An Unusual Focal Task-specific Dystonia?

BACKGROUND: Velopharyngeal dysfunction produces a nasal speech pattern because of the inability to close the nasal airway during speech, most often associated with anatomical abnormalities of the palate. CASE REPORT: We describe two cases of possible velopharyngeal dystonia, a task-specific movement disorder causing a speech pattern similar to velopharyngeal dysfunction. Both patients experienced treatment response with anticholinergic medication. DISCUSSION: Dystonia affecting speech via involvement of the pharyngeal musculature may be an unrecognized etiology of voice disorders.

Speech-Language Pathology Evaluation and Management of Hyperkinetic Disorders Affecting Speech and Swallowing Function.

BACKGROUND: Hyperkinetic dysarthria is characterized by abnormal involuntary movements affecting respiratory, phonatory, and articulatory structures impacting speech and deglutition. Speech-language pathologists (SLPs) play an important role in the evaluation and management of dysarthria and dysphagia. This review describes the standard clinical evaluation and treatment approaches by SLPs for addressing impaired speech and deglutition in specific hyperkinetic dysarthria populations. METHODS: A literature review was conducted using the data sources of PubMed, Cochrane Library, and Google Scholar. Search terms included 1) hyperkinetic dysarthria, essential voice tremor, voice tremor, vocal tremor, spasmodic dysphonia, spastic dysphonia, oromandibular dystonia, Meige syndrome, orofacial, cervical dystonia, dystonia, dyskinesia, chorea, Huntington's Disease, myoclonus; and evaluation/treatment terms: 2) Speech-Language Pathology, Speech Pathology, Evaluation, Assessment, Dysphagia, Swallowing, Treatment, Management, and diagnosis. RESULTS: The standard SLP clinical speech and swallowing evaluation of chorea/Huntington's disease, myoclonus, focal and segmental dystonia, and essential vocal tremor typically includes 1) case history; 2) examination of the tone, symmetry, and sensorimotor function of the speech structures during non-speech, speech and swallowing relevant activities (i.e., cranial nerve assessment); 3) evaluation of speech characteristics; and 4) patient self-report of the impact of their disorder on activities of daily living. SLP management of individuals with hyperkinetic dysarthria includes behavioral and compensatory strategies for addressing compromised speech and intelligibility. Swallowing disorders are managed based on individual symptoms and the underlying pathophysiology determined during evaluation. DISCUSSION: SLPs play an important role in contributing to the differential diagnosis and management of impaired speech and deglutition associated with hyperkinetic disorders.

Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency.

BACKGROUND: Arginine:glycine amidinotransferase deficiency (AGAT-d) is a very rare inborn error of creatine synthesis mainly characterized by absence of brain Creatine (Cr) peak, intellectual disability, severe language impairment and behavioural disorder and susceptible to supplementary Cr treatment per os. Serial examinations by magnetic resonance spectroscopy are required to evaluate Cr recovery in brain during treatment of high doses of Cr per os, which have been proved beneficial and effective in treating main clinical symptoms. A long term study with detailed reports on clinical, neurochemical and neuropsychological outcomes of the first Italian patients affected by AGAT-d here reported can represent a landmark in management of this disorder thus enhancing medical knowledge and clinical practice. RESULTS: We have evaluated the long term effects of Cr supplementation management in four Italian patients affected by AGAT-d, correlating specific treatments with serial clinical, biochemical and magnetic resonance spectroscopy examinations as well as the neuropsychological outcome by standardized developmental scales. Consecutive MRS examinations have confirmed that Cr depletion in AGAT-d patients is reversible under Cr supplementation. Cr treatment is considered safe and well tolerated but side effects, including weight gain and kidney stones, have been reported. CONCLUSIONS: Early treatment prevents adverse developmental outcome, while patients diagnosed and treated at an older age showed partial but significant cognitive recovery with clear improvements in adaptive functioning.

Longitudinal follow-up to evaluate speech disorders in early-treated patients with infantile-onset Pompe disease.

BACKGROUND: Patients with infantile-onset Pompe disease (IOPD) can be treated by recombinant human acid alpha glucosidase (rhGAA) replacement beginning at birth with excellent survival rates, but they still commonly present with speech disorders. This study investigated the progress of speech disorders in these early-treated patients and ascertained the relationship with treatments. METHODS: Speech disorders, including hypernasal resonance, articulation disorders, and speech intelligibility, were scored by speech-language pathologists using auditory perception in seven early-treated patients over a period of 6 years. Statistical analysis of the first and last evaluations of the patients was performed with the Wilcoxon signed-rank test. RESULTS: A total of 29 speech samples were analyzed. All the patients suffered from hypernasality, articulation disorder, and impairment in speech intelligibility at the age of 3 years. The conditions were stable, and 2 patients developed normal or near normal speech during follow-up. Speech therapy and a high dose of rhGAA appeared to improve articulation in 6 of the 7 patients (86%, p = 0.028) by decreasing the omission of consonants, which consequently increased speech intelligibility (p = 0.041). Severity of hypernasality greatly reduced only in 2 patients (29%, p = 0.131). CONCLUSION: Speech disorders were common even in early and successfully treated patients with IOPD; however, aggressive speech therapy and high-dose rhGAA could improve their speech disorders.

Utilization Patterns of Topical Intranasal Steroid Therapy for Chronic Rhinosinusitis: A Canadian Population-Based Analysis.

Importance: Practice guidelines have provided a strong recommendation for the daily use of topical intranasal steroid therapy for patients with chronic rhinosinusitis (CRS). Deficiencies in utilization of intranasal steroid therapy may represent a gap in quality of care. Objective: To evaluate the utilization patterns of topical intranasal steroid therapy for CRS in the Canadian population. Design, Setting, and Participants: Retrospective review of a Canadian population-based health care administrative database. A validated case definition for CRS was applied, and the utilization of topical intranasal steroid therapy within this cohort was quantified during the 2014-2015 fiscal year. Interventions: Intranasal steroid spray for CRS. Main Outcomes and Measures: Primary outcome was the rate (per 100 patients) and quantity (per patient) of intranasal steroid spray utilization in patients with CRS. Secondary outcome was the geographic variation in the rate and quantity of intranasal steroid spray utilization for CRS. Results: A total of 19 057 adult patients with CRS were evaluated. The overall rate of intranasal steroid spray utilization was 20.1 per 100 patients with CRS (3821 of 19 057). In the 3821 patients with CRS who used an intranasal steroid spray during 2014 to 2015, the mean quantity of utilization was 2.4 U (1 U = 1 bottle per month) per patient (9314 U divided by 3821 patients with CRS). There was large geographic variation in both the rate and quantity of intranasal steroid spray utilization (P < .001 for both comparisons). Conclusions and Relevance: Topical intranasal steroid therapy continues to be underutilized for patients with CRS. Given the negative impact of low-quality medical care, outcomes from this study indicate a need to further evaluate factors leading to the underutilization of a recommended treatment in patients with CRS to improve overall health system performance.

[The efficacy of tenoten for children in the treatment of motor and speech disorders in children with perinatal damage of the central nervous system]. / Effektivnost' tenotena detskogo pri motornykh i rechevykh narusheniyakh u detei, perenesshikh perinatal'noe porazhenie tsentral'noi nervnoi sistemy.

AIM: To assess the therapeutic efficacy of tenoten for children in perinatal hypoxic CNS damage in children. MATERIAL AND METHODS: The study included 80 children (56 boys and 24 girls) between the ages of 3 and 3 years and 11 months with different variants (dysontogenetic or encephalopathic) of the effects on the perinatal nervous system. All children were divided into primary (n=50) and control (n=30) groups. Children of the primary group received a combination of conventional speech therapy methods with tenoten for children (1 tablet 3 times a day for 12 weeks). In the control group, children were not treated with tenoten for children. RESULTS AND CONCLUSION: The inclusion of tenoten in a comprehensive children's speech therapy program contributed significantly to the successful development of both general motor skills and spatial coordination as well as fine motor skills in the hand. In addition, tenoten significantly decreased signs of dysarthria and improved articulation, specifically in children with dysontogenetic variant of perinatal hypoxic CNS damage. Tenoten had a positive effect on child's behavior as well.

Impact of Parkinson's disease and levodopa on resting state functional connectivity related to speech prosody control.

BACKGROUND: Impaired speech prosody is common in Parkinson's disease (PD). We assessed the impact of PD and levodopa on MRI resting-state functional connectivity (rs-FC) underlying speech prosody control. METHODS: We studied 19 PD patients in the OFF and ON dopaminergic conditions and 15 age-matched healthy controls using functional MRI and seed partial least squares correlation (PLSC) analysis. In the PD group, we also correlated levodopa-induced rs-FC changes with the results of acoustic analysis. RESULTS: The PLCS analysis revealed a significant impact of PD but not of medication on the rs-FC strength of spatial correlation maps seeded by the anterior cingulate (p = 0.006), the right orofacial primary sensorimotor cortex (OF_SM1; p = 0.025) and the right caudate head (CN; p = 0.047). In the PD group, levodopa-induced changes in the CN and OF_SM1 connectivity strengths were related to changes in speech prosody. CONCLUSIONS: We demonstrated an impact of PD but not of levodopa on rs-FC within the brain networks related to speech prosody control. When only the PD patients were taken into account, the association between treatment-induced changes in speech prosody and changes in rs-FC within the associative striato-prefrontal and motor speech networks was found.

Verbal Fluencies and Fampridine Treatment in Multiple Sclerosis.

BACKGROUND/AIMS: Fampridine is sometimes reported to improve cognition and especially the information-processing speed. Motor improvement might be a confounding factor. The aim of this study was to evaluate the effects of fampridine on verbal fluencies in patients with multiple sclerosis (MS). METHODS: Fifty MS patients were included in a prospective monocentric open label trial with a mean Expanded Disability Status Scale of 5.3 ± 1.1. Assessments of verbal phonological and semantic fluencies were repeated twice (within 1 week) before fampridine treatment and twice after fampridine treatment in order to have the maximal practice effect. Gait velocity and fatigue (visual analogical scale) were also assessed. Distribution into gait responders, gait non-responders, fluency responders and fluency non-responders, was described. RESULTS: Verbal fluencies were significantly higher after fampridine treatment. No correlation was observed between phonological fluency improvement and semantic fluency improvement. Gait responders and gait non-responders did not present significant differences in verbal fluency performance and fatigue score. No correlation between gait velocity improvement and fatigue improvement compared with verbal fluency improvement was observed. CONCLUSION: Our results suggest that fampridine could have a selective procognitive effect on phonological fluency in MS, even in the gait non-responder patients.

A role for risperidone in the treatment of communication disorder and comorbid mental health problems?

This case report describes the co-occurrence of a psychiatric disorder with a specific communication disorder in a teenage girl who presented to youth mental health services in crisis, posing a significant risk of harm to herself and others. Description of this case would be of interest to practitioners in youth mental health in relation to the assessment and treatment of young people with similar difficulties. We present the case of a 17-year-old girl previously admitted to an inpatient adolescent unit. Her diagnosis was reformulated 4 months into her second admission to include a specific communication disorder with both receptive and expressive difficulties, evident from her pragmatic use of language. She was started on risperidone in month eight; following this, a significant improvement was seen and the patient was discharged a month later. Prior to the start of risperidone, a referral had been made to low secure adolescent services for further assessment and advice on management, due to the patient's challenging presentation and poor engagement with treatment.

Neuropharmacology of Poststroke Motor and Speech Recovery.

Almost 7 million adult Americans have had a stroke. There is a growing need for more effective treatment options as add-ons to conventional therapies. This article summarizes the published literature for pharmacologic agents used for the enhancement of motor and speech recovery after stroke. Amphetamine, levodopa, selective serotonin reuptake inhibitors, and piracetam were the most commonly used drugs. Pharmacologic augmentation of stroke motor and speech recovery seems promising but systematic, adequately powered, randomized, and double-blind clinical trials are needed. At this point, the use of these pharmacologic agents is not supported by class I evidence.

Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide.

BACKGROUND: Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis. OBJECTIVE: We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition. RESULTS: 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100-800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions. CONCLUSION: AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing.

[Intracranial sinus venous thrombosis in ulcerative colitis. Report of one case]. / Trombosis de senos venosos intracraneales: una complicación infrecuente y grave de la colitis ulcerosa. Primera comunicación de un caso en Uruguay.

Intracranial sinus venous thrombosis (ICSVT) is a rare complication of ulcerative colitis that affects from 1.7 to 7.5% of patients. We report a 22 year-old male with ulcerative colitis in treatment with mesalazine and prednisone presenting with headache and speech disturbances. A magnetic resonance imaging of the brain showed a left temporal hemorrhagic infarct with thrombosis of the ispilateral superficial vein and sigmoid venous sinus. No cause of thrombophilia was detected. Anticoagulation with heparin was started which was changed to oral anticoagulation with warfarin. The patient was discharged ten days after admission.

Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free L-arginine in humans.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis, whereas L-arginine (Arg) and L-homoarginine (hArg) serve as substrates for NO synthesis. ADMA and other methylated arginines are generally believed to exclusively derive from guanidine (N (G))-methylated arginine residues in proteins by protein arginine methyltransferases (PRMTs) that use S-adenosylmethionine (SAM) as the methyl donor. L-Lysine is known for decades as a precursor for hArg, but only recent studies indicate that arginine:glycine amidinotransferase (AGAT) is responsible for the synthesis of hArg. AGAT catalyzes the formation of guanidinoacetate (GAA) that is methylated to creatine by guanidinoacetate methyltransferase (GAMT) which also uses SAM. The aim of the present study was to learn more about the mechanisms of ADMA and hArg formation in humans. Especially, we hypothesized that ADMA is produced by N (G)-methylation of free Arg in addition to the known PRMTs-involving mechanism. In knockout mouse models of AGAT- and GAMT-deficiency, we investigated the contribution of these enzymes to hArg synthesis. Arg infusion (0.5 g/kg, 30 min) in children (n = 11) and ingestion of high-fat protein meals by overweight men (n = 10) were used to study acute effects on ADMA and hArg synthesis. Daily Arg ingestion (10 g) or placebo for 3 or 6 months by patients suffering from peripheral arterial occlusive disease (PAOD, n = 20) or coronary artery disease (CAD, n = 30) was used to study chronic effects of Arg on ADMA synthesis. Mass spectrometric methods were used to measure all biochemical parameters in plasma and urine samples. In mice, AGAT but not GAMT was found to contribute to plasma hArg, while ADMA synthesis was independent of AGAT and GAMT. Arg infusion acutely increased plasma Arg, hArg and ADMA concentrations, but decreased the plasma hArg/ADMA ratio. High-fat protein meals acutely increased plasma Arg, hArg, ADMA concentrations, as well as the plasma hArg/ADMA ratio. In the PAOD and CAD studies, plasma Arg concentration increased in the verum compared to the placebo groups. Plasma ADMA concentration increased only in the PAOD patients who received Arg. Our study suggests that in humans a minor fraction of free Arg is rapidly metabolized to ADMA and hArg. In mice, GAMT and N (G)-methyltransferases contribute to ADMA and hArg synthesis from Arg, whereas AGAT is involved in the synthesis of hArg but not of ADMA. The underlying biochemical mechanisms remain still elusive.

[The effect of cellex on cognitive and speech impairments in the acute stage of stroke].

OBJECTIVE: To study the effect of cellex on the recovery of cognitive and speech functions in the acute stage of stroke. MATERIAL AND METHODS: A multicenter comparative open clinical study of the efficacy and safety of cellex in treatment of patients with acute stroke was carried out in 6 clinical sites. The study involved 180 patients, including 147 (81.7%) with ischemic stroke and 33 (18.3%) with hemorrhagic stroke. Celex was introduced subcutaneously in dose 0.1 mg once a day during the first 10 days and from 21 to 27th days. RESULTS AND CONCLUSION: The rapid and complete recovery of neurological and cognitive functions was observed. The more marked dynamics was seen in patients with greater initial stroke severity and with large hemisphere lesions.

Trombosis de senos venosos intracraneales: una complicación infrecuente y grave de la colitis ulcerosa. Primera comunicación de un caso en Uruguay / Intracranial sinus venous thrombosis in ulcerative colitis: Report of one case

Intracranial sinus venous thrombosis (ICSVT) is a rare complication of ulcerative colitis that affects from 1.7 to 7.5% of patients. We report a 22 year-old male with ulcerative colitis in treatment with mesalazine and prednisone presenting with headache and speech disturbances. A magnetic resonance imaging of the brain showed a left temporal hemorrhagic infarct with thrombosis of the ispilateral superficial vein and sigmoid venous sinus. No cause of thrombophilia was detected. Anticoagulation with heparin was started which was changed to oral anticoagulation with warfarin. The patient was discharged ten days after admission.

Effect of dopaminergic medication on speech dysfluency in Parkinson's disease: a longitudinal study.

Although speech dysfluencies have been hypothesized to be associated with abnormal function of dopaminergic system, the effects of dopaminergic medication on speech fluency in Parkinson's disease (PD) have not been systematically studied. The aim of the present study was, therefore, to investigate the long-term effect of dopaminergic medication on speech fluency in PD. Fourteen de novo PD patients with no history of developmental stuttering and 14 age- and sex-matched healthy controls (HC) were recruited. PD subjects were examined three times; before the initiation of dopaminergic treatment and twice in following 6 years. The percentage of dysfluent words was calculated from reading passage and monolog. The amount of medication was expressed by cumulative doses of L-dopa equivalent. After 3-6 years of dopaminergic therapy, PD patients exhibited significantly more dysfluent events compared to healthy subjects as well as to their own speech performance before the introduction of dopaminergic therapy (p < 0.05). In addition, we found a strong positive correlation between the increased occurrence of dysfluent words and the total cumulative dose of L-dopa equivalent (r = 0.75, p = 0.002). Our findings indicate an adverse effect of prolonged dopaminergic therapy contributing to the development of stuttering-like dysfluencies in PD. These findings may have important implication in clinical practice, where speech fluency should be taken into account to optimize dopaminergic therapy.