Journal of Clinical Medicine

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Clinical Management of Movement Disorders

by Lazzaro di Biase

J. Clin. Med. 2024, 13(1), 43; https://doi.org/10.3390/jcm13010043 - 21 Dec 2023

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Abstract

Movement disorders include a wide and heterogeneous variety of signs and syndromes, which are classified as hyperkinetic [...] Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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16 pages, 2155 KiB

Open AccessArticle

Differences in the Time Course of Recovery from Brain and Liver Dysfunction in Conventional Long-Term Treatment of Wilson Disease

by Harald Hefter, Theodor S. Kruschel, Max Novak, Dietmar Rosenthal, Tom Luedde, Sven G. Meuth, Philipp Albrecht, Christian J. Hartmann and Sara Samadzadeh

J. Clin. Med. 2023, 12(14), 4861; https://doi.org/10.3390/jcm12144861 - 24 Jul 2023

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Abstract

Background: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized [...] Read more.

Background: The aim of this study was to demonstrate that both neurological and hepatic symptoms respond to copper chelation therapy in Wilson disease (WD). However, the time course of their recovery is different. Methods: Eighteen patients with neurological WD from a single specialized center who had been listed for liver transplantation during the last ten years and two newly diagnosed homozygous twins were recruited for this retrospective study. The mean duration of conventional treatment was 7.3 years (range: 0.25 to 36.2 years). A custom Wilson disease score with seven motor items, three non-motor items, and 33 biochemical parameters of the blood and urine, as well as the MELD score, was determined at various checkup visits during treatment. These data were extracted from the charts of the patients. Results: Treatment was initiated with severity-dependent doses (≥900 mg) of D-penicillamine (DPA) or triethylene-tetramin-dihydrochloride (TRIEN). The motor score improved in 10 and remained constant in 8 patients. Worsening of neurological symptoms was observed only in two patients who developed comorbidities (myasthenia gravis or hemispheric stroke). The neurological symptoms continuously improved over the years until the majority of patients became only mildly affected. In contrast to this slow recovery of the neurological symptoms, the MELD score and liver enzymes had already started to improve after 1 month and rapidly improved over the next 6 months in 19 patients. The cholinesterase levels continued to increase significantly (p < 0.0074) even further. One patient whose MELD score indicated further progression of liver disease received an orthotopic liver transplantation 3 months after the diagnosis of WD and the onset of DPA treatment. Conclusions: Neurological and hepatic symptoms both respond to copper chelation therapy. For patients with acute liver failure, the first 4 months are critical. This is the time span in which patients have to wait either for a donor organ or until significant improvement has occurred under conventional therapy. For patients with severe neurological symptoms, it is important that they are treated with fairly high doses over several years. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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11 pages, 2805 KiB

Open AccessArticle

Treatment Changes and Prognoses in Patients with Incident Drug-Induced Parkinsonism Using a Korean Nationwide Healthcare Claims Database

by Siin Kim and Hae Sun Suh

J. Clin. Med. 2023, 12(8), 2860; https://doi.org/10.3390/jcm12082860 - 13 Apr 2023

Cited by 1 | Viewed by 1668

Abstract

This retrospective cohort study assessed treatment changes and prognoses after incident drug-induced parkinsonism (DIP). We used the National Health Insurance Service’s National Sample Cohort database in South Korea. We selected patients diagnosed with incident DIP and given prescriptions to take offending drugs (antipsychotics, [...] Read more.

This retrospective cohort study assessed treatment changes and prognoses after incident drug-induced parkinsonism (DIP). We used the National Health Insurance Service’s National Sample Cohort database in South Korea. We selected patients diagnosed with incident DIP and given prescriptions to take offending drugs (antipsychotics, gastrointestinal (GI) motility drugs, or flunarizine) for a period of time that overlapped with the time of DIP diagnosis during 2004–2013. The proportion of patients experiencing each type of treatment change and prognosis was assessed for 2 years after DIP diagnosis. We identified 272 patients with incident DIP (51.9% of patients were aged ≥ 60 years and 62.5% of them were women). Switching (38.4%) and reinitiation (28.8%) were the most common modifications in GI motility drug users, whereas dose adjustment (39.8%) and switching (23.0%) were common in antipsychotic users. The proportion of persistent users was higher among antipsychotic users (7.1%) than that among GI motility drug users (2.1%). Regarding prognosis, 26.9% of patients experienced DIP recurrence or persistence, the rate being the highest in persistent users and the lowest in patients who discontinued the drug. Among patients with incident DIP diagnoses, the patterns of treatment change and prognosis differed across the types of offending drugs. Over 25% of patients experienced DIP recurrence or persistence, highlighting the need for an effective strategy to prevent DIP. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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14 pages, 1756 KiB

Open AccessArticle

The Impact of Nonmotor Symptoms on Health-Related Quality of Life in Parkinson’s Disease: A Network Analysis Approach

by Konstantin G. Heimrich, Aline Schönenberg, Diego Santos-García, Pablo Mir, COPPADIS Study Group and Tino Prell

J. Clin. Med. 2023, 12(7), 2573; https://doi.org/10.3390/jcm12072573 - 29 Mar 2023

Cited by 7 | Viewed by 2440

Abstract

Nonmotor symptoms negatively affect health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD). However, it is unknown which nonmotor symptoms are most commonly associated with HRQoL. Considering the complex interacting network of various nonmotor symptoms and HRQoL, this study aimed to [...] Read more.

Nonmotor symptoms negatively affect health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD). However, it is unknown which nonmotor symptoms are most commonly associated with HRQoL. Considering the complex interacting network of various nonmotor symptoms and HRQoL, this study aimed to reveal the network structure, explained HRQoL variance, and identify the nonmotor symptoms that primarily affect HRQoL. We included 689 patients with PD from the Cohort of Patients with Parkinson’s Disease in Spain (COPPADIS) study who were rated on the Nonmotor Symptoms Scale in Parkinson’s disease (NMSS) and the Parkinson´s Disease Questionnaire 39 (PDQ-39) at baseline. Network analyses were performed for the 30 items of the NMSS and both the PDQ-39 summary index and eight subscales. The nodewise predictability, edge weights, strength centrality, and bridge strength were determined. In PD, nonmotor symptoms are closely associated with the mobility, emotional well-being, cognition, and bodily discomfort subscales of the PDQ-39. The most influential nonmotor symptoms were found to be fatigue, feeling sad, hyperhidrosis, impaired concentration, and daytime sleepiness. Further research is needed to confirm whether influencing these non-motor symptoms can improve HRQoL. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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9 pages, 1674 KiB

Open AccessArticle

Quantitative High Density EEG Brain Connectivity Evaluation in Parkinson’s Disease: The Phase Locking Value (PLV)

by Lazzaro di Biase, Lorenzo Ricci, Maria Letizia Caminiti, Pasquale Maria Pecoraro, Simona Paola Carbone and Vincenzo Di Lazzaro

J. Clin. Med. 2023, 12(4), 1450; https://doi.org/10.3390/jcm12041450 - 11 Feb 2023

Cited by 12 | Viewed by 2493

Abstract

Introduction: The present study explores brain connectivity in Parkinson’s disease (PD) and in age matched healthy controls (HC), using quantitative EEG analysis, at rest and during a motor tasks. We also evaluated the diagnostic performance of the phase locking value (PLV), a measure [...] Read more.

Introduction: The present study explores brain connectivity in Parkinson’s disease (PD) and in age matched healthy controls (HC), using quantitative EEG analysis, at rest and during a motor tasks. We also evaluated the diagnostic performance of the phase locking value (PLV), a measure of functional connectivity, in differentiating PD patients from HCs. Methods: High-density, 64-channels, EEG data from 26 PD patients and 13 HC were analyzed. EEG signals were recorded at rest and during a motor task. Phase locking value (PLV), as a measure of functional connectivity, was evaluated for each group in a resting state and during a motor task for the following frequency bands: (i) delta: 2–4 Hz; (ii) theta: 5–7 Hz; (iii) alpha: 8–12 Hz; beta: 13–29 Hz; and gamma: 30–60 Hz. The diagnostic performance in PD vs. HC discrimination was evaluated. Results: Results showed no significant differences in PLV connectivity between the two groups during the resting state, but a higher PLV connectivity in the delta band during the motor task, in HC compared to PD. Comparing the resting state versus the motor task for each group, only HCs showed a higher PLV connectivity in the delta band during motor task. A ROC curve analysis for HC vs. PD discrimination, showed an area under the ROC curve (AUC) of 0.75, a sensitivity of 100%, and a negative predictive value (NPV) of 100%. Conclusions: The present study evaluated the brain connectivity through quantitative EEG analysis in Parkinson’s disease versus healthy controls, showing a higher PLV connectivity in the delta band during the motor task, in HC compared to PD. This neurophysiology biomarkers showed the potentiality to be explored in future studies as a potential screening biomarker for PD patients. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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10 pages, 1270 KiB

Open AccessArticle

Treatment of Dystonic Tremor of the Upper Limbs: A Single-Center Retrospective Study

by Belén González-Herrero, Ilaria Antonella Di Vico, Erlick Pereira, Mark Edwards and Francesca Morgante

J. Clin. Med. 2023, 12(4), 1427; https://doi.org/10.3390/jcm12041427 - 10 Feb 2023

Cited by 2 | Viewed by 2402

Abstract

Tremor is part of the phenomenological spectrum of dystonia. Treatments available for tremor in dystonia are oral medications (OM), botulinum neurotoxin (BoNT), and brain surgery (deep brain stimulation or thalamotomy). There is limited knowledge regarding the outcome of different treatment options, and evidence [...] Read more.

Tremor is part of the phenomenological spectrum of dystonia. Treatments available for tremor in dystonia are oral medications (OM), botulinum neurotoxin (BoNT), and brain surgery (deep brain stimulation or thalamotomy). There is limited knowledge regarding the outcome of different treatment options, and evidence is especially scarce for the tremor of the upper limbs occurring in people with dystonia. In this single-center retrospective study, we evaluated the outcome of different treatments in a cohort of people with upper limb dystonic tremors. Demographic, clinical, and treatment data were analyzed. Dropout rates and side effects were specifically assessed, as well as the 7-point patient-completed clinical global impression scale (p-CGI-S, 1: very much improved; 7: very much worse) as outcome measures. A total of 47 subjects (46.8% female) with dystonic tremor, tremor associated with dystonia, or task-specific tremor were included, with a median age at onset of 58 years (7–86). A total of 31 subjects were treated with OM, 31 with BoNT, and 7 with surgery. Dropout rates with OM were 74.2% due to either lack of efficacy (n = 10) or side effects (n = 13). A total of 7 patients treated with BoNT (22.6%) had mild weakness, causing dropout in 2. P-CGI-S was ≤3 (improvement) in 39% with OM, compared to 92% with BoNT and 100% with surgery. These findings suggest good symptom control of the tremor of the upper limb in dystonia with BoNT and surgery, with higher rates of dropout and side effects with OM. Randomized controlled studies are needed to confirm our findings and provide further insight into better selecting suitable patients for BoNT or brain surgery. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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11 pages, 732 KiB

Open AccessArticle

Efficacy and Safety of Two Salts of Trientine in the Treatment of Wilson’s Disease

by France Woimant, Dominique Debray, Erwan Morvan, Mickael Alexandre Obadia and Aurélia Poujois

J. Clin. Med. 2022, 11(14), 3975; https://doi.org/10.3390/jcm11143975 - 8 Jul 2022

Cited by 12 | Viewed by 2509

Abstract

Background: Wilson’s disease (WD) is one of the few genetic disorders that can be successfully treated with pharmacological agents. Copper-chelating agents (D-penicillamine and Trientine salts) and zinc salts have been demonstrated to be effective. There are two salts of trientine. Trientine dihydrochloride salt [...] Read more.

Background: Wilson’s disease (WD) is one of the few genetic disorders that can be successfully treated with pharmacological agents. Copper-chelating agents (D-penicillamine and Trientine salts) and zinc salts have been demonstrated to be effective. There are two salts of trientine. Trientine dihydrochloride salt (TETA 2HCL) is unstable at room temperature and requires storage at 2–8 °C. Trientine tetrahydrochloride (TETA 4HCL) is a more stable salt of trientine that can be stored at room temperature. No comparative study between both of the salts of trientine has been performed to date. As the two chemical forms were available in France between 1970 and 2009, we conducted a study to evaluate their efficacy and safety profiles. Methods: This retrospective cohort study was conducted by reviewing data from the national WD registry in France. Forty-three WD patients who received TETA 2HCL or TETA 4HCL monotherapy for at least one year until 2010 were included. The primary endpoints were hepatic and neurological outcomes. Secondary endpoints were the events leading to a discontinuation of medication. Results: Changes in medication were common, leading to the analysis of 57 treatment sequences of TETA 4HCL or TETA 2HCL. The mean duration of treatment sequence was significantly longer in the TETA 4 HCL group (12.6 years) than in the TETA 2HCL group (7.6 years) (p = 0.011). Ten patients experienced both trientine salts: eight stopped TETA 4 HCL (six had a hepatologic phenotype and two had a neurological phenotype) because this treatment was not available anymore (mean duration 7.4 years). Three of these patients already experienced TETA 2 HCL before the sequence. Two patients with a hepatologic phenotype (one had a previous sequence of TETA 4 HCL before) stopped TETA 2 HCL because of cold storage issues (mean duration 42.8 years). The total number of sequences was 57. All of the patients were clinically stable. No difference in efficacy was detected. Both treatments were well tolerated, except for a case of recurrence of lupus erythematosus-like syndrome in the TETA 2HCL group. The major reason for interruption of TETA 4HCL was due to a discontinuation in production of this salt. The reasons for stopping TETA 2HCL were mainly due to adherence issues largely attributed to the cold storage requirement. Conclusions: The two salts of trientine were effective in treating patients with WD. However, interruption of TETA 2HCL was frequent, linked to the cold storage requirement. As adherence to treatment is a key factor in the successful management of WD, physicians need to be even more vigilant in detecting adherence difficulties in patients receiving treatment with TETA 2HCL. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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28 pages, 4226 KiB

Open AccessArticle

Gait Characterization and Analysis of Hereditary Amyloidosis Associated with Transthyretin Patients: A Case Series

by Maria do Carmo Vilas-Boas, Pedro Filipe Pereira Fonseca, Inês Martins Sousa, Márcio Neves Cardoso, João Paulo Silva Cunha and Teresa Coelho

J. Clin. Med. 2022, 11(14), 3967; https://doi.org/10.3390/jcm11143967 - 7 Jul 2022

Cited by 2 | Viewed by 1637

Abstract

Hereditary amyloidosis associated with transthyretin (ATTRv), is a rare autosomal dominant disease characterized by length-dependent symmetric polyneuropathy that has gait impairment as one of its consequences. The gait pattern of V30M ATTRv amyloidosis patients has been described as similar to that of diabetic [...] Read more.

Hereditary amyloidosis associated with transthyretin (ATTRv), is a rare autosomal dominant disease characterized by length-dependent symmetric polyneuropathy that has gait impairment as one of its consequences. The gait pattern of V30M ATTRv amyloidosis patients has been described as similar to that of diabetic neuropathy, associated with steppage, but has never been quantitatively characterized. In this study we aim to characterize the gait pattern of patients with V30M ATTRv amyloidosis, thus providing information for a better understanding and potential for supporting diagnosis and disease progression evaluation. We present a case series in which we conducted two gait analyses, 18 months apart, of five V30M ATTRv amyloidosis patients using a 12-camera, marker based, optical system as well as six force platforms. Linear kinematics, ground reaction forces, and angular kinematics results are analyzed for all patients. All patients, except one, showed a delayed toe-off in the second assessment, as well as excessive pelvic rotation, hip extension and external transverse rotation and knee flexion (in stance and swing phases), along with reduced vertical and mediolateral ground reaction forces. The described gait anomalies are not clinically quantified; thus, gait analysis may contribute to the assessment of possible disease progression along with the clinical evaluation. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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16 pages, 929 KiB

Open AccessReview

Deep Brain Stimulation in the Treatment of Tardive Dyskinesia

by Adrianna Szczakowska, Agata Gabryelska, Oliwia Gawlik-Kotelnicka and Dominik Strzelecki

J. Clin. Med. 2023, 12(5), 1868; https://doi.org/10.3390/jcm12051868 - 27 Feb 2023

Cited by 4 | Viewed by 4431

Abstract

Tardive dyskinesia (TD) is a phenomenon observed following the predominantly long-term use of dopamine receptor blockers (antipsychotics) widely used in psychiatry. TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid, lips, tongue, and cheeks, and [...] Read more.

Tardive dyskinesia (TD) is a phenomenon observed following the predominantly long-term use of dopamine receptor blockers (antipsychotics) widely used in psychiatry. TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning and, moreover, causing stigmatization and suffering. Deep brain stimulation (DBS), a method used, among others, in Parkinson’s disease, is also an effective treatment for TD and often becomes a method of last resort, especially in severe, drug-resistant forms. The group of TD patients who have undergone DBS is still very limited. The procedure is relatively new in TD, so the available reliable clinical studies are few and consist mainly of case reports. Unilateral and bilateral stimulation of two sites has proven efficacy in TD treatment. Most authors describe stimulation of the globus pallidus internus (GPi); less frequent descriptions involve the subthalamic nucleus (STN). In the present paper, we provide up-to-date information on the stimulation of both mentioned brain areas. We also compare the efficacy of the two methods by comparing the two available studies that included the largest groups of patients. Although GPi stimulation is more frequently described in literature, our analysis indicates comparable results (reduction of involuntary movements) with STN DBS. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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13 pages, 803 KiB

Open AccessReview

Motor Skills and Visual Deficits in Developmental Coordination Disorder: A Narrative Review

by Elena Pinero-Pinto, Rita Pilar Romero-Galisteo, María Carmen Sánchez-González, Isabel Escobio-Prieto, Carlos Luque-Moreno and Rocío Palomo-Carrión

J. Clin. Med. 2022, 11(24), 7447; https://doi.org/10.3390/jcm11247447 - 15 Dec 2022

Cited by 5 | Viewed by 3286

Abstract

Background: Developmental coordination disorder (DCD) is a developmental disorder in which numerous comorbidities seem to coexist, such as motor and visual impairment and some executive functions; Methods: A narrative review on motor and visual deficits in children with DCD was carried out; Results [...] Read more.

Background: Developmental coordination disorder (DCD) is a developmental disorder in which numerous comorbidities seem to coexist, such as motor and visual impairment and some executive functions; Methods: A narrative review on motor and visual deficits in children with DCD was carried out; Results and Discussion: Fine and gross motor skills are affected in children with DCD. In addition, they seem to be related to visual deficits, such as difficulty in visual perception, sensory processing and visual memory. Limitations have also been found in accommodation. Interventions in children with DCD should be aimed at improving both aspects, since vision affects motor skills and vice versa; Conclusions: In children with DCD, who present a marked deficit in global shape processing, it causes an association between deficiencies in visual perception and motor skills. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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18 pages, 1471 KiB

Open AccessReview

Dystonia Diagnosis: Clinical Neurophysiology and Genetics

by Lazzaro di Biase, Alessandro Di Santo, Maria Letizia Caminiti, Pasquale Maria Pecoraro, Simona Paola Carbone and Vincenzo Di Lazzaro

J. Clin. Med. 2022, 11(14), 4184; https://doi.org/10.3390/jcm11144184 - 19 Jul 2022

Cited by 10 | Viewed by 5294

Abstract

Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and [...] Read more.

Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and geste antagonists/sensory tricks). Despite advances in research, there is no diagnostic test with a high level of accuracy for the dystonia diagnosis. Clinical neurophysiology and genetics might support the clinician in the diagnostic process. Neurophysiology played a role in untangling dystonia pathophysiology, demonstrating characteristic reduction in inhibition of central motor circuits and alterations in the somatosensory system. The neurophysiologic measure with the greatest evidence in identifying patients affected by dystonia is the somatosensory temporal discrimination threshold (STDT). Other parameters need further confirmations and more solid evidence to be considered as support for the dystonia diagnosis. Genetic testing should be guided by characteristics such as age at onset, body distribution, associated features, and coexistence of other movement disorders (parkinsonism, myoclonus, and other hyperkinesia). The aim of the present review is to summarize the state of the art regarding dystonia diagnosis focusing on the role of neurophysiology and genetic testing. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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21 pages, 2790 KiB

Open AccessReview

The Patho-Neurophysiological Basis and Treatment of Focal Laryngeal Dystonia: A Narrative Review and Two Case Reports Applying TMS over the Laryngeal Motor Cortex

by Maja Rogić Vidaković, Ivana Gunjača, Josipa Bukić, Vana Košta, Joško Šoda, Ivan Konstantinović, Braco Bošković, Irena Bilić and Nikolina Režić Mužinić

J. Clin. Med. 2022, 11(12), 3453; https://doi.org/10.3390/jcm11123453 - 15 Jun 2022

Cited by 2 | Viewed by 2539

Abstract

Focal laryngeal dystonia (LD) is a rare, idiopathic disease affecting the laryngeal musculature with an unknown cause and clinically presented as adductor LD or rarely as abductor LD. The most effective treatment options include the injection of botulinum toxin (BoNT) into the affected [...] Read more.

Focal laryngeal dystonia (LD) is a rare, idiopathic disease affecting the laryngeal musculature with an unknown cause and clinically presented as adductor LD or rarely as abductor LD. The most effective treatment options include the injection of botulinum toxin (BoNT) into the affected laryngeal muscle. The aim of this narrative review is to summarize the patho-neuro-physiological and genetic background of LD, as well as the standard recommended therapy (BoNT) and pharmacological treatment options, and to discuss possible treatment perspectives using neuro-modulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and vibrotactile stimulation. The review will present two LD cases, patients with adductor and abductor LD, standard diagnostic procedure, treatments and achievement, and the results of cortical excitability mapping the primary motor cortex for the representation of the laryngeal muscles in the assessment of corticospinal and corticobulbar excitability. Full article

(This article belongs to the Special Issue Clinical Management of Movement Disorders)

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