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European Journal of Paediatric... May 2024GLUT1 deficiency syndrome (GLUT1DS) is a rare genetic disorder caused by a mutation in the SLC2A1 gene that limits the transport of glucose across the blood-brain...
RESEARCH PURPOSE
GLUT1 deficiency syndrome (GLUT1DS) is a rare genetic disorder caused by a mutation in the SLC2A1 gene that limits the transport of glucose across the blood-brain barrier. Speech disorders and dysarthria are typical findings in patients with GLUT1DS, but have never been deeply phenotyped. The aim of the present study was to characterize speech abilities in a sample of patients with GLUT1DS.
RESULTS
30 patients with GLUT1DS were recruited. We reported impairments in different speech and oromotor domains: the speech was characterized by dysarthria, inaccurate articulation of consonants, abnormal nasal resonance, errors in intonation and prosody and low intelligibility. We observed difficulties in motor planning and programming. Moreover, we observed a significant difference between the dysarthric level of impairment with genotype groups.
CONCLUSIONS
The presence of a speech disorder in patients with GLUT1DS represents a core feature of the syndrome. Our findings suggest that patients with GLUT1DS would benefit from a comprehensive neurocognitive assessment to detect strengths and weaknesses of the speech profile. Understanding the speech and language phenotype in GLUT1DS is critical for planning early intervention to positively influence the global development of patients with GLUT1DS.
PubMed: 38851145
DOI: 10.1016/j.ejpn.2024.05.010 -
Annals of Medicine and Surgery (2012) Jun 2024Spinocerebellar ataxias (SCAs) are a rare autosomal dominant neurodegenerative disorder. To date, approximately 50 different subtypes of SCAs have been characterized.... (Review)
Review
Spinocerebellar ataxias (SCAs) are a rare autosomal dominant neurodegenerative disorder. To date, approximately 50 different subtypes of SCAs have been characterized. The prevalent types of SCAs are usually of PolyQ origin, wherein the disease pathology is a consequence of multiple glutamine residues being encoded onto the disease proteins, causing expansions. SCAs 2 and 3 are the most frequently diagnosed subtypes, wherein affected patients exhibit certain characteristic physiological manifestations, such as gait ataxia and dysarthria. Nevertheless, other clinical signs were exclusive to these subtypes. Recently, multiple molecular diagnostic methods have been developed to identify and characterize these subtypes. Despite these advancements, the molecular pathology of SCAs remains unknown. To further understand the mechanisms involved in neurodegenerative SCAs 2 and 3, patient-derived induced pluripotent stem cell (iPSC)-based modelling is a compelling avenue to pursue. We cover the present state of iPSC-based in-vitro illness modelling of SCA subtypes 2 and 3 below, along with a list of cell lines created, and the relevance of research outcomes to personalized autologous therapy.
PubMed: 38846892
DOI: 10.1097/MS9.0000000000001984 -
Brain Communications 2024Up to half of all people with multiple sclerosis experience communication difficulties due to dysarthria, a disorder that impacts the motor aspects of speech production....
Up to half of all people with multiple sclerosis experience communication difficulties due to dysarthria, a disorder that impacts the motor aspects of speech production. Dysarthria in multiple sclerosis is linked to cerebellar dysfunction, disease severity and lesion load, but the neuroanatomical substrates of these symptoms remain unclear. In this study, 52 participants with multiple sclerosis and 14 age- and sex-matched healthy controls underwent structural and diffusion MRI, clinical assessment of disease severity and cerebellar dysfunction and a battery of motor speech tasks. Assessments of regional brain volume and white matter integrity, and their relationships with clinical and speech measures, were undertaken. White matter tracts of interest included the interhemispheric sensorimotor tract, cerebello-thalamo-cortical tract and arcuate fasciculus, based on their roles in motor and speech behaviours. Volumetric analyses were targeted to Broca's area, Wernicke's area, the corpus callosum, thalamus and cerebellum. Our results indicated that multiple sclerosis participants scored worse on all motor speech tasks. Fixel-based diffusion MRI analyses showed significant evidence of white matter tract atrophy in each tract of interest. Correlational analyses further indicated that higher speech naturalness-a perceptual measure of dysarthria-and lower reading rate were associated with axonal damage in the interhemispheric sensorimotor tract and left arcuate fasciculus in people with multiple sclerosis. Axonal damage in all tracts of interest also correlated with clinical scales sensitive to cerebellar dysfunction. Participants with multiple sclerosis had lower volumes of the thalamus and corpus callosum compared with controls, although no brain volumetrics correlated with measures of dysarthria. These findings indicate that axonal damage, particularly when measured using diffusion metrics, underpin dysarthria in multiple sclerosis.
PubMed: 38846538
DOI: 10.1093/braincomms/fcae177 -
Cureus May 2024The anti-CASPR2 antibody-associated syndrome is a rare immune-mediated disorder. Most case reports describe neurologic symptoms that include encephalic signs,...
The anti-CASPR2 antibody-associated syndrome is a rare immune-mediated disorder. Most case reports describe neurologic symptoms that include encephalic signs, peripheral nerve hyperexcitability, dysautonomia, or neuropathic pain. We report the case of a 70-year-old man, admitted to the emergency department with complaints of slurred speech and imbalance. Neurological examination was relevant for dysarthria, hyperreflexia, and pancerebellar syndrome. Cranial CT and basic laboratory tests were normal and he spontaneously recovered after 14 hours. Over the next four months, the patient experienced three similar episodes in relation to stressful events (emotional and organic disturbances like prolonged fasting and vaccination). A contrast-enhanced MRI was performed, along with extensive laboratory testing, analysis of cerebrospinal fluid (CSF), paraneoplastic investigation, and next-generation sequencing panel for episodic ataxias. The results revealed oligoclonal bands in the CSF and positive anti-CASPR2 antibodies both in serum and CSF. Three-day-IV- methylprednisolone pulse followed by plasmapheresis and monthly intravenous immunoglobulins was performed with good response. In conclusion, the neurological manifestations that led to the diagnosis of anti-CASPR2 antibody-associated syndrome were intermittent self-limiting episodes of ataxia, often triggered by concurrent stress-inducing factors. This case supports the aim of other authors to add paroxysmal cerebellar ataxia to the spectrum of the anti-CASPR2 antibody syndrome.
PubMed: 38846209
DOI: 10.7759/cureus.59821 -
Molecular Genetics and Metabolism Jun 2024Information about dysarthria and dysphagia in mitochondrial diseases (MD) is scarce. However, this knowledge is needed to identify speech and swallowing problems early,...
BACKGROUND
Information about dysarthria and dysphagia in mitochondrial diseases (MD) is scarce. However, this knowledge is needed to identify speech and swallowing problems early, to monitor the disease course, and to develop and offer optimal treatment and support. This study therefore aims to examine the prevalence and severity of dysarthria and dysphagia in patients with MD and its relation to clinical phenotype and disease severity. Secondary aim is to determine clinically relevant outcome measures for natural history studies and clinical trials.
METHODS
This retrospective cross-sectional medical record study includes adults (age ≥ 18 years) diagnosed with genetically confirmed MD who participated in a multidisciplinary admission within the Radboud center for mitochondrial medicine between January 2015 and April 2023. Dysarthria and dysphagia were examined by administering the Radboud dysarthria assessment, swallowing speed, dysphagia limit, test of mastication and swallowing solids (TOMASS), and 6-min mastication test (6MMT). The disease severity was assessed using the Newcastle mitochondrial disease scale for adults (NMDAS).
RESULTS
The study included 224 patients with MD with a median age of 42 years of whom 37.5% were male. The pooled prevalence of dysarthria was 33.8% and of dysphagia 35%. Patients with MD showed a negative deviation from the norm on swallowing speed, TOMASS (total time) and the 6MMT. Furthermore, a significant moderate relation was found between the presence of dysarthria and the clinical phenotypes. There was a statistically significant difference in total time on the TOMASS between the clinical phenotypes. Finally, disease severity showed a significant moderate relation with the severity of dysarthria and a significant weak relation with the severity of dysphagia.
CONCLUSION
Dysarthria and dysphagia occur in about one-third of patients with MD. It is important for treating physicians to pay attention to this subject because of the influence of both disorders on social participation and wellbeing. Referral to a speech and language therapist should therefore be considered, especially in patients with a more severe clinical phenotype. The swallowing speed, TOMASS and 6MMT are the most clinically relevant tests to administer.
PubMed: 38843620
DOI: 10.1016/j.ymgme.2024.108510 -
Turk Psikiyatri Dergisi = Turkish... 2024Lithium may cause toxicity as it has a narrow therapeutic range. Lithium intoxication may manifest in the form of acute, acute on chronic and chronic intoxication....
Lithium may cause toxicity as it has a narrow therapeutic range. Lithium intoxication may manifest in the form of acute, acute on chronic and chronic intoxication. Neurotoxicity is a common component of chronic lithium intoxication and the symptoms include tremor, ataxia, dysarthria, extrapyramidal symptoms, hyperreflexia, seizures and status epilepticus. Although rare, catatonia could as a manifestation of lithium neurotoxicity. In this report, we present a patient with bipolar disorder presenting with catatonic symptoms secondary to lithium intoxication. We will discuss the risk factors, differential diagnosis and the treatment of catatonic symptoms. Lithium neurotoxicity may present with various clinical symptoms including catatonia, and differential diagnosis should be made well in such cases. If lithium neurotoxicity is suspected, rapid and appropriate intervention is required to prevent permanent neurological damage. Keywords: Lithium, Neurotoxicity, Catatonia.
Topics: Humans; Antimanic Agents; Bipolar Disorder; Catatonia; Diagnosis, Differential; Neurotoxicity Syndromes
PubMed: 38842156
DOI: 10.5080/u27074 -
Neurology. Genetics Jun 2024Facial-onset sensory and motor neuronopathy (FOSMN) is a rare neuromuscular disorder characterized by progressive facial sensory impairment followed by motor dysfunction...
OBJECTIVES
Facial-onset sensory and motor neuronopathy (FOSMN) is a rare neuromuscular disorder characterized by progressive facial sensory impairment followed by motor dysfunction in a rostro-caudal distribution. FOSMN is clinically and pathologically associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). In contrast to ALS/FTD, the genetic profile of patients with FOSMN and the role of genetic testing are poorly defined.
METHODS
A 66-year-old woman was evaluated in our neuromuscular clinic for progressive facial pain, dysphagia, and dysarthria. Her diagnostic evaluation included brain and cervical MRI, nerve conduction studies and EMG, and an ALS/FTD next-generation sequencing panel.
RESULTS
The patient was diagnosed with FOSMN, and we identified a N390D variant in transactive response DNA-binding protein (TDP-43/). This variant has never been reported in FOSMN but was previously reported in 2 cases of ALS, and a N390S variant was also previously reported in FOSMN. A review of the literature revealed that mutations are overrepresented in patients with FOSMN compared with patients with ALS/FTD. By contrast, other common familial forms of ALS, including or , are respectively absent or rare in FOSMN.
DISCUSSION
FOSMN is pathologically and genetically associated with TDP-43. Therefore, ALS genetic testing that includes specifically should be considered in patients with FOSMN.
PubMed: 38841627
DOI: 10.1212/NXG.0000000000200160 -
Cureus May 2024Marchiafava-Bignami disease (MBD) is a rare demyelinating disease associated with chronic alcohol use and/or malnutrition leading to vitamin deficiency. Clinical...
Marchiafava-Bignami disease (MBD) is a rare demyelinating disease associated with chronic alcohol use and/or malnutrition leading to vitamin deficiency. Clinical presentation is diverse and can range from mild neurological deficits of dysarthria and confusion to severe symptoms such as coma or even death. Diagnosis is made using imaging modalities including magnetic resonance imaging (MRI) and computed tomography (CT) with the rise in technological advances placing MRI as the most sensitive and specific imaging technology for diagnosis. Classic MBD imaging demonstrates demyelination and necrotic damage of the corpus callosum. While MBD is a well-documented neurologic complication of chronic alcoholism, its occurrence and presentation in the context of concurrent polysubstance abuse remain underexplored. We outline the case of a 27-year-old male with polysubstance use disorder presenting with subacute neurological deterioration and demyelination of the splenium of the corpus callosum.
PubMed: 38841043
DOI: 10.7759/cureus.59730 -
American Journal of Speech-language... Jun 2024This study investigated the effects of the SPEAK OUT! & LOUD Crowd therapy program on speaking rate, percent pause time, intelligibility, naturalness, and communicative...
PURPOSE
This study investigated the effects of the SPEAK OUT! & LOUD Crowd therapy program on speaking rate, percent pause time, intelligibility, naturalness, and communicative participation in individuals with Parkinson's disease (PD).
METHOD
Six adults with PD completed 12 individual SPEAK OUT! sessions across four consecutive weeks followed by group-based LOUD Crowd sessions for five consecutive weeks. Most therapy sessions were conducted via telehealth, with two participants completing the SPEAK OUT! portion in person. Speech samples were recorded at six time points: three baseline time points prior to SPEAK OUT!, two post-SPEAK OUT! time points, and one post-LOUD Crowd time point. Acoustic measures of speaking rate and percent pause time and listener ratings of speech intelligibility and naturalness were obtained for each time point. Participant self-ratings of communicative participation were also collected at pre- and posttreatment time points.
RESULTS
Results showed significant improvement in communicative participation scores at a group level following completion of the SPEAK OUT! & LOUD Crowd treatment program. Two participants showed a significant decrease in speaking rate and increase in percent pause time following treatment. Changes in intelligibility and naturalness were not statistically significant.
CONCLUSIONS
These findings provide preliminary support for the effectiveness of the SPEAK OUT! & LOUD Crowd treatment program in improving communicative participation for people with mild-to-moderate hypokinetic dysarthria secondary to PD. This study is also the first to demonstrate positive effects of this treatment program for people receiving the therapy via telehealth.
PubMed: 38838243
DOI: 10.1044/2024_AJSLP-23-00321