ObjectivePost-stroke dysarthria (DYS) severely affects communication, yet cortical morphological alterations remain insufficiently characterized. This study applied surface-based morphometry (SBM) to examine cortical changes in DYS and their association with dysarthria severity assessed by the Frenchay Dysarthria Assessment (FDA).MethodsForty-eight DYS patients and 72 matched controls underwent MRI. Cortical fractal dimension and gyrification were extracted via SBM. Group differences were tested using two-sample t-tests, and correlations with FDA scores were assessed using Spearman analyses.ResultsDYS patients exhibited significantly increased fractal dimension in the left insula and elevated gyrification in bilateral insula, superior temporal and precentral gyri (p < 0.05). Right supramarginal gyrification positively correlated with FDA reflex and respiration subscores (ρ > 0.3, p < 0.05). No significant differences were observed between supratentorial and infratentorial lesions.ConclusionCortical morphological alterations in insula and supramarginal gyrus may contribute to DYS pathophysiology. SBM provides quantitative markers linking cortical architecture to speech motor control, potentially guiding individualized rehabilitation strategies.

El SARS-CoV-2, responsable de la pandemia actual, es un β-coronavirus que se une al receptor de ECA- 2 para infectar a la célula diana. Fiebre, tos y disnea son los síntomas más comunes. Los síntomas neurológicos están cobrando gran interés por su asociación con infección pulmonar, invasión directa del virus al Sistema Nervioso Central o de aparición pos-infección. En este reporte, se describe el caso de un paciente masculino de 52 años de edad, hipertenso y diabético tipo 2, con clínica clásica de Síndrome de Guillain Barré al ingreso y clínica respiratoria 15 días previos a la instalación de los síntomas neurológicos. Igualmente, con pruebas serológicas para SARS-CoV-2 positivas en dos oportunidades, además del antecedente epidemiológico de contacto directo con personas infectadas por SARS-CoV-2 confirmadas. Lenguaje disártrico, disfonía, diplejía facial, cuadriparesia y arreflexia destacaron como hallazgos al examen físico. Fue trasladado a UCI por disnea, mas no requirió ventilación mecánica y se le administró inmunoglobulina humana resultando mejoría significativa. Se tomó muestra de hisopado nasofaríngeo a los 23 días del inicio de la enfermedad actual para RT-PCR que resultó negativa. Se discute el tipo y calidad de la muestra, fase de la enfermedad en la que se toma el espécimen y la experticia del operador como determinantes de la sensibilidad de la prueba. Aunque el resultado fue negativo, es claro el diagnóstico clínico y epidemiológico para SARS-CoV-2. Según la revisión de la literatura, este es el primer caso de Guillain Barré pos-infección de SARS-CoV-2 reportado en Venezuela hasta el presente.

This brief preliminary article suggests the use of pitch analysis for gaining insight in the mechanisms of dysarthria affecting specific subjects, when dysarthria involves poor control of the vocal cords. Examples are provided.

Objective To understand the incidences of adverse reactions on cognition, language, and bone metabolism related to 8 commonly used antiepileptic drugs in China using SIDER database. Methods The integrated incidences of adverse reactions on cognition, language, and bone metabolism related to 8 commonly used antiepileptic drugs (carbamazepine, oxcarbazepine, valproate, clonazepam, lamotrigine, levetiracetam, topiramate, and zonisamide) marketed in China was searched in the SIDER database. Results The main drugs that affected cognition were topiramate and valproate. The incidences of memory impairment caused by topiramate and abnormal thinking related to valproate were 1.2%-10.8% and 6.0%, respectively. Topiramate was the main drug that affected language. The incidences of dysarthria and speech disorder caused by topiramate were 1.6%-6.2% and 1.0%-16.8%, respectively. The main antiepileptic drugs that affected bone metabolism were carbamazepine, oxcarbazepine, and valproate. But there was no incidence information because of the limited small amount of literature reports after marketing. Conclusions The results of data analysis in this database indicate that different antiepileptic drugs have different effects on cognitive function, language function and bone metabolism, and the frequency of adverse reactions is different. The clinical use of antiepileptic drugs needs to weigh the advantages and disadvantages according to the specific situation of patients. Key words: Drug-related side effects and adverse reactions; Epilepsy; Anticonvulsants; Cognition; Language; Osteoporosis; Fractures, bone

Data of the VPD study in the research is included in this data set.

Objective To discuss the multiple system involvement and cranial magnetic resonance imaging(MRI) manifestations of Wilson disease(WD) in children. Methods This study was conducted on hospitalized children who were diagnosed as WD at the Department of Pediatrics, Peking University First Hospital during January 2001 to December 2017, and their clinical data were reviewed. Results Sixty-five children were enrolled, among whom 28 cases were of neurological type, while 37 cases were of non-neurological type.The average onset age of neurological type was 11.0 years old, while non-neurological type was 8.1 years old(t=3.328, P=0.001). Seventy-six point nine percent children had at least 2 systems involved, among which the liver and the brain were the most commonly involved, while the involvement in the urinary and the blood systems were not scarce(55.4% and 33.8%, respectively). Among K-F ring, ceruloplasmin and 24-hour urinary copper excretion, 17.2% of the cases had 2 of the three items normal, and 13.8% had 1 item normal.K-F ring positive could be seen in all neurological type, while the positive rate was 57.6% in non-neurological type, and the difference was statistically significant(χ2=13.981, P<0.001). The average age of K-F ring positive patients was(11.8±2.7)years old, while it was (7.6±3.7)years old in K-F ring negative patients, and the difference was statistically significant(t=4.221, P<0.001). There was no statistic diffe-rence in 24- hour urinary copper excretion between neurologic and non-neurologic type(t=0.024, P=0.981). The most common neurologic symptoms included dysarthria, tremor, drooling/swallowing/chewing problems, abnormal postures, etc.Basal ganglia, white matter involvement, brain atrophy and ventricle enlargement in cranial MRI could all be seen in both types, and basal ganglia was the most commonly involved site, but the thalamus and the brain stem could only be seen in neurologic type.Among 30 patients with abnormal cranial MRI patients, the earliest onset age of basal ganglia, ventricle enlargement, brain atrophy, and white matter involvement were all at 8 years old, while the earliest onset age of the thalamus and the brain stem involvement was at 12 years old.The longer the course of neurological symptoms, the more involvement could be found in the thalamus and the brain stem. Conclusions WD always present with multi-systems involvement, with a variety of clinical manifestations.One or two normal characters among K-F ring, ceruloplasmin and 24-hour urinary copper excretion could not exclude WD.Cranial MRI abnormalities could present earlier than neurological symptoms.Basal ganglia was the most commonly involved, while the thalamus and the brain stem were involved later, mostly in their adolescents. Key words: Wilson disease; Retrospective study; K-F ring; Cranial magnetic resonance imaging; Child

In “IgLON5-mediated neurodegeneration is a differential diagnosis of CNS Whipple disease,” Morales-Briceno et al. described a case of anti-IgLON5 disease presenting as cold intolerance, myorhythmia, myoclonus, dysarthria, hypersalivation, dysphagia, sleep apnea, and mildly impaired cognition mimicking CNS Whipple disease. Drs. Bally and Lang report that the presentation in this case was similar to cases of Whipple disease in the literature; however, palatal involvement of the myorhythmia—which was present in the case reported by Morales-Briceno et al.—is rare in Whipple disease, and the cranial myorhythmia in Whipple disease is associated with a vertical supranuclear gaze palsy, which was not present in the case reported by Morales-Briceno et al. Morales-Briceno et al. respond that while the absence of vertical gaze palsy made Whipple disease less likely, such gaze palsies can occur in a certain percentage of patients with IgLON5-mediated neurodegeneration. Both Morales-Briceno et al. and Drs. Bally and Lang agree that the distinction between IgLON5-mediated neurodegeneration and Whipple disease can be challenging. In “IgLON5-mediated neurodegeneration is a differential diagnosis of CNS Whipple disease,” Morales-Briceno et al. described a case of anti-IgLON5 disease presenting as cold intolerance, myorhythmia, myoclonus, dysarthria, hypersalivation, dysphagia, sleep apnea, and mildly impaired cognition mimicking CNS Whipple disease. Drs. Bally and Lang report that the presentation in this case was similar to cases of Whipple disease in the literature; however, palatal involvement of the myorhythmia—which was present in the case reported by Morales-Briceno et al.—is rare in Whipple disease, and the cranial myorhythmia in Whipple disease is associated with a vertical supranuclear gaze palsy, which was not present in the case reported by Morales-Briceno et al. Morales-Briceno et al. respond that while the absence of vertical gaze palsy made Whipple disease less likely, such gaze palsies can occur in a certain percentage of patients with IgLON5-mediated neurodegeneration. Both Morales-Briceno et al. and Drs. Bally and Lang agree that the distinction between IgLON5-mediated neurodegeneration and Whipple disease can be challenging.

Using Crowdsourced Listeners’ Ratings to Measure Speech Changes in Hypokinetic Dysarthria

Objective To investigate the clinical features, polysomnography, imaging examination, genetic analysis and laboratory examination of eight patients with familial fatal insomnia (FFI). Methods The clinical data, neuropsychological examination, results of cerebrospinal fluid analysis, imaging examination and polysomnography of eight patients with FFI in Xuanwu Hospital, Capital Medical University from 2009 to 2018 were retrospectively analyzed and summarized. Results Among the eight FFI patients, there were 3 males and 5 females, the onset age being (49.8±14.3) years (19 to 64 years) and the course of disease being eight to 18 months. D178N mutation in the PRNP gene of chromosome 20 and 129 amino acid polymorphisms of M/M were found in genetic examination in all the eight patients, of which five patients had family history. All the patients had sleep disorders, sleep-related involuntary movement, sleep-related dyspnea, laryngeal stridor. All the patients showed rapid progressive dementia with or without symptoms or signs of psychosis, ataxia, pyramidal and extrapyramidal. All the eight patients had progressive sympathetic symptoms, including hypertension, sweating, tachycardia, irregular breathing, and dysarthria. Cerebrospinal fluid 14-3-3 protein was found positive in one patient, and negative in seven patients. Electroencephalograph showed diffuse slow wave and non periodic synchronous discharge. Single-photon emission computed tomography or 18F fluorodeoxyglucose positron emission tomography showed decreased thalamic glucose metabolism in three patients. Seven patients showed decreased total sleep time, sleep awakening cycle disorder, especially the reduction or loss of rapid eye movement, laryngeal stridor and involuntary movement in polysomnography. Conclusions FFI is characterized by sleep disorder, sleep-related involuntary movement, dyspnea, laryngosis, rapid progressive dementia and sympathetic symptoms. The family history, polysomnography and positron emission tomography are helpful for the diagnosis of FFI. PRNP gene detection can confirm the diagnosis of FFI. Key words: Insomnia, fatal familial; Dementia; Polysomnography; PRNP gene

Дослідження дизартрії у дорослих при хворобі Паркінсона

発声・発語には頭頚部諸筋の運動が関与している．運動系は上位運動ニューロン，下位運動ニューロンを経て筋へ興奮伝達する経路を主体とし，その途中で大脳基底核・小脳を中心とした制御系によって協調運動が遂行される．dysarthriaはそれらの障害によって生じる．dysarthriaは高位診断と対応してpyramidal，extrapyramidal，ataxic，flaccidに分類される．pyramidal dysarthriaは上位運動ニューロン障害によって生じ痙性麻痺を呈する．extrapyramidal dysarthriaは大脳基底核障害で，hypokineticとhyperkineticに分けられる．ataxic dysarthriaは小脳系の障害によって生じる．flaccid dysarthriaは下位運動ニューロン以遠の障害によって生じる．

Analysis of Preceding Studies in Korea on the Acoustic Analysis of Patients with Dysarthria Using Praat

Objective To report the clinical features, myopathological changes, and gene mutations in five Chinese patients with mitochondrial diseases caused by POLG gene mutations. Methods Clinical materials of five unrelated patients who were referred to Department of Neurology, Peking University First Hospital from April 2012 to January 2018, carrying POLG gene mutations, were retrospectively analyzed. Muscle/nerve biopsies and targeted second-generation gene sequencing were performed on the patients. Results Among the five patients, three were male and two were female. Two cases were dominant inheritance and three were sporadic or recessive inheritance. The ages of onset were from 15 to 40 years with disease course of one to 26 years. One of them showed atypical SANDO (sensory ataxic neuropathy, dysarthria, and ophthalmoparesis) syndrome accompanied by cardiac preexcitation syndrome. There were two cases with autosomal dominant and one case with recessive progressive external ophthalmoplegia plus syndrome. One case presented with cognitive delay and sensory neuropathy. The pathological changes of mitochondrial myopathy were observed in all four patients with muscle involvement. Sural nerve biopsy in the patient with cognitive delay and sensory ataxia revealed chronic axonal pathological changes. POLG gene mutations were found in all five patients by targeted next generation sequencing, including single heterozygous mutations in two dominant inherited patients (c.914 G>A and c.2864A>G, respectively), and compound heterozygous POLG gene mutations in the other three sporadic/recessive inherited patients (c.2591 A>G/c.1790 G>A, c.924G>T/c.3002delG and c.1613A>T/c.1612 G>T, respectively). There were six novel mutations not reported before, i.e., c.914G>A(p.S305N), c.924G>T(p.Q308H), c.1613A>T(p.E538V), c.1612G>T(p.E538*), c.1790 G>A(p.R597Q) and c.3002delG. Conclusions POLG gene mutations can lead to different clinical spectrums. Progressive external ophthalmoplegia, limb weakness and axonal sensory neuropathy are common presentations in this group of patients with POLG gene related mitochondrial neuromuscular diseases. Novel mutations found in this study expand the mutational spectrum of POLG gene. Key words: Mitochondrial disease; DNA polymerase gamma; POLG gene; Progressive external ophthalmoplegia; Axonal sensory neuropathy

A 36 year-old female patient with stage II invasive mole (low-risk type) received single drug chemotherapy with 5-fluorouracil (5-Fu). The 5-Fu (30 mg/kg) was given by an intravenous infusion from the first day to the eighth day in each 22-day chemotherapy cycle. The patient developed dysarthria and dysphagia during the 5-Fu treatment on day 6 in the third cycle. The result of head magnetic resonance imaging (MRI) showed extensive white matter injury. 5-Fu was immediately discontinued and nutritional supportive treatments to brain cells were given. Five hours later, the above symptoms disappeared. Twenty-four hours later, the above symptoms recurred and above-mentioned supportive treatments were given again. Three hours after the treatment, the above symptoms disappeared again. Then the chemotherapy regimen was changed to be an IV infusion of actinomycin D (0.4 mg/d) from the first day to the fifth day in each 19-day cycle. During the treatment, the patient′s vital signs were stable and her pronunciation and ingurgitation functions were normal. Key words: Hydatidiform mole, invasive; Fluorouracil; Leukoencephalopathies

Objective To report the clinical and paraclinical features of a case series with anti-IgLON5 antibody related encephalopathy. Methods One hundred and fifty patients with sleep disorders and subacute or chronic onset of movement disorders, parkinsonism or bulbar palsy were included. The serum and cerebrospinal fluid specimens of these patients were screened for anti-IgLON5 antibody. The clinical and paraclinical features of patients with seropositive anti-IgLON5 antibody were summarized. Results Three patients with seropositive anti-IgLON5 antibody were identified, with one female and two males. The onset age ranged from 61 to 64 years. Case 1 presented with symptoms of involuntary movement, unsteady walk and insomnia; case 2 with symptoms of insomnia, sleep behavioral disorder, psychiatric behavior and dysphagia; case 3 with symptoms of insomnia, sleep behavioral disorder, dysarthria, and tremor. When examined by polysomnography, obstructive sleep apnea syndrome was revealed in cases 1 and 2, serious insomnia was found in cases 2 and 3, and sleep behavioral disorder was revealed in case 2. All three patients were positive for HLA-DQB1*0501, and cases 2 and 3 were positive for HLA-DRB1*1001. All three patients received immunotherapy and only one patient (case 1) responded well to immunotherapy with intravenous immunoglobulin, steroids and mycophenolate mofetil. Conclusions Anti-IgLON5-related encephalopathy is a rare disease with distinct clinical features of both autoimmune disorders and neurodegeneration disorders. These patients may benefit from immunotherapy. Key words: Autoantibodies; Tauopathy; Brain diseases; Sleep disorders; Immunotherapy

We report the case of an 8-year-old boy with delayed psychomotor development, dysarthria, choreoathetosis, joint mild hyperlaxity, coarse hair, dry lax skin and facial dimorphisms. Cerebral magnetic resonance revealed diffuse vascular tortuosity, with multiple loops in some arteries of Willis ’ circle. Clinical presentation, corroborated by the imagiological findings, raised the suspicion of a disorder of copper metabolism. Serum copper and ceruloplasmin were decreased and lateral skull X-rays demonstrated bilateral occipital exostoses. ATP7A gene sequencing identified a hemizygous variant c.375delA (p.Ala126Glnfs*2), confirming the diagnosis of occipital horn syndrome. Occipital horn syndrome (also called X-linked cutis laxa) is a milder form of Menkes disease. This rare disorder of copper metabolism results from mutations in ATP7A gene encoding a transmembrane copper-transporting enzyme. The broad spectrum of clinical presentation makes the diagnosis challenging. This case illustrates the importance of a multidisciplinary approach, highlighting the role of neuroimaging. J Med Cases. 2018;9(7):207-210 doi: https://doi.org/10.14740/jmc3078w

Introduction. Acute Disseminated Encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder, usually triggered by an infection, which affects the brain and spinal cord. Because this disease affects the white matter, patients may present with behavioral changes or alterations in consciousness. In this case, atypical diffuse demyelination of the brain rather than multiple, patchy lesions appears to have affected cardiac and autonomic function by an unknown mechanism. Case Report. A 14-year-old previously healthy female presented with ataxia, slow dysarthric speech, and blurry vision progressively worsening over one month. One day prior she had a …

Objective To investigate the early efficacy of deep brain stimulation (DBS) of subthalamic nucleus (STN) in the treatment of dysarthria in patients with Parkinson's disease (PD). Methods From May 2017 to November 2017, 10 PD patients treated with STN-DBS at Neurosurgery Department affiliated to Nanjing Medical University and 10 healthy volunteers (healthy control group) were recruited retrospectively. Ten PD patients without anti-Parkinson disease medication were recorded in a relatively quiet room at the states of 1 month after operation with stimulation-off, 1 month after operation with stimulation-on, and 3 months after stimulation-on. The speech signal was analyzed by Praat software and 3 fundamental frequency parameters were extracted which were the mean fundamental frequency, the range and standard deviation of fundamental frequency. The speech signals from the healthy control subjects were collected and analyzed at the same time. Results The speech fundamental frequency range (PD group: 15.5±4.8 St, control group: 22.5±5.6 St, t=-2.962, P=0. 008) and the standard deviation of fundamental frequency (PD group: 2.4±0.7 St, control group: 3.7±0.8 St, t=-4.017, P=0. 001) in PD group with stimulation-off 1 month post operation were significantly lower than those in healthy control group. There was no significant difference in any parameter of fundamental frequency of the PD patients between the state of 1 month after stimulation-on and the state of 1 month after operation (all P > 0.05). At 3 months after stimulation-on, the fundamental frequency range (19.23.8 St, P=0.017) and the fundamental frequency standard deviation (3.20.8 St, P=0.001) of the speech were significantly higher than those at 1 month after operation with stimulation-off, and those was not significant statistical different compared with controls (all P > 0.05). Conclusion Early stage of STN-DBS treatment could improve the phonological tone of PD patients and relieve the stiffness of laryngeal muscles and vocal cord. Key words: Parkinson disease; Dysarthria; Deep brain stimulation; Subthalamic nucleus; Acoustic analysis

A 23-year old female presented in the Emergency Department with dysarthria, bradykinesia and ataxia. The patient inhaled heroin one week before the onset of the symptoms. She was tachypnoeic but haemodynamically stable (blood pressure 145/90 mm Hg) with a normal sinus rhythm. Corneal reflexes were present bilaterally and the motor examination revealed axial myoclonus. General examination revealed no cardiac murmurs whilst the chest and abdomen were unremarkable. No needle marks were observed on the skin. After a normal initial brain computed tomography (CT) scan, the patient was further evaluated with brain magnetic resonance imaging (MRI) A second MRI was performed after a 13 day hospitalisation.

Tumours of the brainstem account for approximately 10% to 15% of all central nervous system (CNS) neoplasms in children, with diffuse intrinsic pontine glioma (DIPG) being the most common type. Affected patients with DIPG are mostly children at the age of 5 to 10-years-old. While brainstem gliomas may arise in other parts of the brainstem including the midbrain and medulla oblongata with a more favourable prognosis, pontine location is very frequent with a typically aggressive disease cause leading to a limited lifespan for the affected patients. Patients with DIPG may present with cranial nerve symptoms due to compression and dysfunction of nuclei and tracts located in the pons. A wide spectrum of symptoms may occur including impaired vision and diplopia, nausea and vomiting, headache, impaired alignment of the eyes, gait disturbances, dysarthria, facial asymmetry or weakness, impaired communication with altered levels of consciousness, changes in behaviour, impaired mobility, spasticity, weakness in legs and arms. Brainstem gliomas located at the pons with diffuse and extensive infiltration are typically not amenable for complete surgical resection. In this context, radiation therapy (RT) has traditionally been the mainstay of treatment for DIPG. Optimal radiation dose and fractionation and combined modality management with RT and chemotherapy has been the focus of extensive research over several decades. Herein, we assess the utility of RT for DIPG management in light of the literature.