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Parkinsonism & Related Disorders Apr 2024Deep brain stimulation (DBS) surgery is an established and effective treatment for several movement disorders (tremor, Parkinson's disease, and dystonia), and is under... (Review)
Review
Deep brain stimulation (DBS) surgery is an established and effective treatment for several movement disorders (tremor, Parkinson's disease, and dystonia), and is under investigation in numerous other neurological and psychiatric disorders. However, the origins and development of this neurofunctional technique are not always well understood and recognized. In this mini-review, we review the history of DBS, highlighting important milestones and the most remarkable protagonists (neurosurgeons, neurologists, and neurophysiologists) who pioneered and fostered this therapy throughout the 20th and early 21st century. Alongside DBS historical markers, we also briefly discuss newer developments in the field, and the future challenges which accompany such progress.
Topics: Humans; Deep Brain Stimulation; Tremor; Parkinson Disease; Dystonia; Neurosurgeons
PubMed: 38161106
DOI: 10.1016/j.parkreldis.2023.105980 -
Current Opinion in Otolaryngology &... Oct 2023To summarize the treatment options available for the management of postparalytic facial synkinesis which include facial rehabilitation, chemodenervation, and a spectrum... (Review)
Review
PURPOSE OF REVIEW
To summarize the treatment options available for the management of postparalytic facial synkinesis which include facial rehabilitation, chemodenervation, and a spectrum of surgical interventions.
RECENT FINDINGS
Facial rehabilitation and botulinum toxin chemodenervation represent the foundation of facial synkinesis management, with specific treatment paradigms directed by individual patient needs. Evolving surgical approaches range from isolated selective myectomies or neurectomies to combination approaches which may incorporate various types of nerve transfer with gracilis free muscle transplantation.
SUMMARY
Postparalytic facial synkinesis bears significant patient morbidity due to aesthetic and functional implications. Management strategies must balance patient goals with treatment risks and typically progress stepwise from the least to most invasive interventions. Emerging techniques reveal a convergence in approaches to facial reanimation and synkinesis mitigation.
Topics: Humans; Synkinesis; Botulinum Toxins; Esthetics; Face; Nerve Transfer
PubMed: 37610981
DOI: 10.1097/MOO.0000000000000920 -
Ugeskrift For Laeger Sep 2023Palatal tremor (PT) is a rare cause of objective tinnitus. Symptomatic PT is caused by injuries of the Guillain-Mollaret triangle with contraction of levator veli...
Palatal tremor (PT) is a rare cause of objective tinnitus. Symptomatic PT is caused by injuries of the Guillain-Mollaret triangle with contraction of levator veli palatini. Essential PT causes are unknown and is produced by contraction of tensor veli palatini, with pathognomonic audible ear click. This is a case report of a 36-year-old female, who developed bilateral objective tinnitus, as well as vertigo, blepharospasm, and neck tension after a free fall trauma 30 metres in the net. She was diagnosed with essential PT and treated with botulinum neurotoxin injections in the soft palate.
Topics: Female; Humans; Adult; Tinnitus; Tremor; Palatal Muscles; Palate, Soft; Myoclonus
PubMed: 37767868
DOI: No ID Found -
Physiotherapy Theory and Practice Jul 2023Balance impairments are common in cerebellar ataxia. Exercises are beneficial in this population. (Meta-Analysis)
Meta-Analysis
Effects of therapeutic exercise on disease severity, balance, and functional Independence among individuals with cerebellar ataxia: A systematic review with meta-analysis.
BACKGROUND
Balance impairments are common in cerebellar ataxia. Exercises are beneficial in this population.
OBJECTIVE
Explore the benefits of therapeutic exercises on disease severity, balance and functional independence in cerebellar ataxia.
METHODS
Databases were searched from inception until July 2021. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale and the Newcastle-Ottawa Scale (NOS); and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.
RESULTS
Twenty-six studies were included and eight studies of low to high PEDro methodological quality were meta-analyzed. 'Low' to 'moderate' GRADE quality evidence supports the use of therapeutic exercises to reduce disease severity, assessed using the Scale for the Assessment and Rating of Ataxia [weighted mean difference (WMD): -3.3; 95% confidence interval (95%CI): -3.7, -2.8; p < .01]; and improve balance, assessed using the Berg Balance Scale (WMD: 2.6; 95%CI: 1.1, 4.2; p < .01). The effect of therapeutic exercises on functional independence was insignificant (WMD: 1.6; 95%CI: -1.5, 4.6; p = .31).
CONCLUSION
Low to moderate evidence from studies of low to high methodological quality provides some support for therapeutic exercises for reducing disease severity among non-hereditary degenerative cerebellar ataxia and improving balance among acquired cerebellar ataxia. Exercises did not benefit functional independence. Additional studies of large sample size and high methodological quality are necessary to substantiate these findings.
Topics: Humans; Cerebellar Ataxia; Functional Status; Exercise Therapy; Exercise; Ataxia; Patient Acuity
PubMed: 35212247
DOI: 10.1080/09593985.2022.2037115 -
Arquivos de Neuro-psiquiatria Nov 2023Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration... (Review)
Review
BACKGROUND
Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia.
OBJECTIVE
To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases.
METHODS
We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022.
RESULTS
Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia.
CONCLUSION
Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.
Topics: Humans; Spastic Paraplegia, Hereditary; Mutation; Tremor; Dystonia; Movement Disorders; Ataxia; Parkinsonian Disorders; Proteins
PubMed: 38035585
DOI: 10.1055/s-0043-1777005 -
Ugeskrift For Laeger Sep 2023In this case report, we present a case of a 62-year-old woman with unsteadiness due to CANVAS. In addition to sensory, cerebellar, and vestibular affection she had...
In this case report, we present a case of a 62-year-old woman with unsteadiness due to CANVAS. In addition to sensory, cerebellar, and vestibular affection she had unusual features in the form of chorea and facial dystonia. Moreover, she had cervical dystonia which, to the best of our knowledge, has not previously been reported in CANVAS.
Topics: Female; Humans; Middle Aged; Chorea; Ataxia; Torticollis
PubMed: 37767867
DOI: No ID Found -
Instructional Course Lectures 2024It is important to discuss the importance of synchronous balance between periscapular muscles for scapulothoracic motion and resultant scapulohumeral rhythm....
It is important to discuss the importance of synchronous balance between periscapular muscles for scapulothoracic motion and resultant scapulohumeral rhythm. Abnormalities in this balance can lead to scapular dyskinesia and winging, affecting shoulder motion and leading to impingement. Strategies exist to diagnose and differentiate between pathologies such as muscle paralysis (eg, trapezius or serratus anterior) or overactivity (eg, pectoralis minor). The physician should be aware of the role of diagnostic imaging, as well as the unique considerations for patients with Ehlers-Danlos syndrome. Overall, a comprehensive physical examination to accurately diagnose and treat scapular pathologies is particularly important.
Topics: Humans; Electromyography; Scapula; Shoulder; Muscle, Skeletal; Dyskinesias
PubMed: 38090928
DOI: No ID Found -
The Lancet. Neurology May 2024Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial.
BACKGROUND
Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease.
METHODS
We conducted a phase 3, randomised, double-blind, double-dummy, active-controlled, multicentre trial at 117 academic and community neurology sites in 16 countries, including in Europe, Israel, and the USA. Eligible participants were men and women aged 30 years or older with a diagnosis of Parkinson's disease (Hoehn and Yahr stage ≤3 in the on state) who experienced at least 2·5 h/day of off time. Participants underwent an open-label run-in phase (<12 weeks), during which time optimal regimens were established for both oral immediate-release levodopa-carbidopa and for 24 h/day subcutaneous ND0612 infusion (levodopa-carbidopa 60·0/7·5 mg/mL), with supplemental oral levodopa-carbidopa if needed. Participants were then randomly assigned (1:1) to 12 weeks of double-blind treatment with their optimised regimen of either subcutaneous ND0612 or oral levodopa-carbidopa, with matching oral or subcutaneous placebo given as required to maintain blinding. Randomisation was done via an interactive web response system, stratified by region, using a permuted block schedule. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment group allocation. The primary efficacy endpoint was the change from baseline (ie, time of randomisation, when all patients were receiving an optimised open-label ND0612 regimen) to end of the double-blind phase in total daily on time without troublesome dyskinesia, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT04006210, and is complete.
FINDINGS
Between Sept 30, 2019, and April 8, 2022, 381 participants were enrolled, of whom 259 (68%) were randomly assigned, 128 (49%) to subcutaneous ND0612 and 131 (51%) to oral levodopa-carbidopa. 243 (94%) participants completed the study. Treatment with subcutaneous ND0612 provided an additional 1·72 h (95% CI 1·08 to 2·36) of on time without troublesome dyskinesia compared with oral levodopa-carbidopa (change from baseline of -0·48 h [-0·94 to -0·02] with subcutaneous ND0612 vs -2·20 h [-2·65 to -1·74] with oral levodopa-carbidopa; p<0·0001). Significant treatment differences favouring subcutaneous ND0612 were also found in the first four of nine prespecified hierarchical outcomes of daily off time (-1·40 h [95% CI -1·99 to -0·80]), Movement Disorders Society-Unified Parkinson's Disease Rating Scale part II scores (-3·05 [-4·28 to -1·81]), Patients Global Impression of Change (odds ratio [OR] 5·31 [2·67 to 10·58]), and Clinical Global Impression of Improvement (OR 7·23 [3·57 to 14·64]). Hierarchical testing ended after the fourth secondary endpoint. Adverse events were reported by 287 (89%) of 322 participants during open-label ND0612 optimisation, and by 103 (80%) of 128 in the ND0612 group and 97 (74%) of 131 in the oral levodopa-carbidopa group during the double-blind phase. The most common adverse events were infusion-site reactions (266 [83%] participants during open-label ND0612, and 73 [57%] in the ND0612 group vs 56 [43%] in the oral levodopa-carbidopa group during the double-blind phase), most of which were mild. Serious adverse events in four participants in the ND0612 group were related to study treatment (infusion-site cellulitis [n=2], infusion-site abscess and infusion-site ulcer [n=1]; and paraesthesia and peripheral sensorimotor neuropathy [n=1]). One participant in the ND0612 group died during the double-blind phase, but the death was not related to study treatment (fall leading to traumatic brain injury).
INTERPRETATION
Results of this phase 3 study showed that subcutaneous ND0612 used in combination with oral immediate-release levodopa-carbidopa increased on time without troublesome dyskinesia and reduced off time, with a favourable benefit-risk profile. ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson's disease. The ongoing open-label extension phase will provide further information on the long-term efficacy and safety of treatment.
FUNDING
NeuroDerm.
Topics: Male; Humans; Female; Parkinson Disease; Levodopa; Carbidopa; Antiparkinson Agents; Infusions, Subcutaneous; Dyskinesias; Double-Blind Method; Treatment Outcome
PubMed: 38499015
DOI: 10.1016/S1474-4422(24)00052-8 -
Movement Disorders : Official Journal... Sep 2023
Topics: Humans; Tremor
PubMed: 37718270
DOI: 10.1002/mds.29568 -
Cell Reports. Medicine Oct 2023Dyskinesia is involuntary movement caused by long-term medication with dopamine-related agents: the dopamine agonist 3,4-dihydroxy-L-phenylalanine (L-DOPA) to treat...
Dyskinesia is involuntary movement caused by long-term medication with dopamine-related agents: the dopamine agonist 3,4-dihydroxy-L-phenylalanine (L-DOPA) to treat Parkinson's disease (L-DOPA-induced dyskinesia [LID]) or dopamine antagonists to treat schizophrenia (tardive dyskinesia [TD]). However, it remains unknown why distinct types of medications for distinct neuropsychiatric disorders induce similar involuntary movements. Here, we search for a shared structural footprint using magnetic resonance imaging-based macroscopic screening and super-resolution microscopy-based microscopic identification. We identify the enlarged axon terminals of striatal medium spiny neurons in LID and TD model mice. Striatal overexpression of the vesicular gamma-aminobutyric acid transporter (VGAT) is necessary and sufficient for modeling these structural changes; VGAT levels gate the functional and behavioral alterations in dyskinesia models. Our findings indicate that lowered type 2 dopamine receptor signaling with repetitive dopamine fluctuations is a common cause of VGAT overexpression and late-onset dyskinesia formation and that reducing dopamine fluctuation rescues dyskinesia pathology via VGAT downregulation.
Topics: Mice; Animals; Dopamine Agonists; Levodopa; Dopamine; Antiparkinson Agents; Parkinsonian Disorders; Dyskinesia, Drug-Induced; Oxidopamine; gamma-Aminobutyric Acid
PubMed: 37774703
DOI: 10.1016/j.xcrm.2023.101208