Materiały źródłowe

• #1 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Dystonia is a syndrome of sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal posturing. Cervical dystonia (CD) is a form of dystonia that involves neck muscles. […] Patients with CD are classified according to aetiology into two groups: primary CD (idiopathic–may be genetic or sporadic) or secondary CD (symptomatic). Patients with primary CD have no evidence by history, physical examination or laboratory studies (except primary dystonia gene) of any secondary cause for the dystonic symptoms. CD is a part of either generalised or focal dystonic syndrome which may have a genetic basis, with an identifiable genetic association. Secondary or symptomatic CD may be caused by central or peripheral trauma, exposure to dopamine receptor antagonists (tardive), neurodegenerative disease, and other conditions associated with abnormal functioning of the basal ganglia. In the majority of patients with CD, the aetiology is not identifiable and the disorder is often classified as primary.

• #2 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  Adult-onset idiopathic focal dystonia is the most common type of primary dystonia, and adult-onset idiopathic cervical dystonia (AOICD) is its most prevalent phenotype. […] Increasing evidence indicates that AOICD is a neurophysiological network disorder of GABAergic inhibition, causing a syndrome of dystonia, mood disturbance, and social cognitive dysfunction, with the superior colliculus playing a central role. […] Although classically considered a basal ganglia disorder, it is likely that superior colliculus dysfunction underlies the motor and non-motor symptoms. […] MRI evidence suggest that AOIFD is a network disorder affecting multiple distinct regions in the brain. […] Functionally, the superior colliculus (SC) likely plays a central role in disease mechanism, and this has been corroborated, particularly through utilisation of temporal discrimination.

• #3 Pathophysiology of Dystonia – Dystonia and Speech Motor Control Laboratory

  https://simonyanlab.meei.harvard.edu/research/pathophysiology-of-dystonia/

  Dystonia is a movement disorder of yet unknown causes and pathophysiology. […] Our long-term goal is to identify the neural mechanisms underlying the pathophysiology of focal dystonia and to develop new strategies for enhanced clinical management of this disorder, including its accurate diagnosis, prediction in persons at-risk, and novel therapeutic strategies. […] Despite well-characterized clinical features of LD, its causes and pathophysiology remain unclear. […] Consequently, the absence of objective biomarkers of LD leads to diagnostic inaccuracies, while the lack of understanding of its neural and molecular targets hinders the development of novel therapeutic opportunities for these patients. […] Knowledge obtained from these studies is expected to have a direct clinical impact by establishing enhanced criteria for accurate and objective diagnosis, screening of persons at-risk, and evaluation of mechanism-based novel pharmacological and/or surgical therapies for these patients.

• #4 Dystonia

  https://www.movementdisorders.org/MDS/About/Movement-Disorder-Overviews/Dystonia.htm

  Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. […] The neural mechanism underlying dystonia involves many regions of the central nervous system (particularly: the basal ganglia, cerebellum, supplementary motor areas and sensorimotor cortex) leading to impaired inhibition, abnormal plasticity and sensorimotor dysfunction. […] There are many causes of dystonia. The etiological classification considers two main lines: evidence of nervous system pathology and whether dystonia is inherited or acquired. […] In many cases of isolated dystonia there is no evidence of degeneration or structural lesion (e.g., DYT1, DYT6; formerly called „primary” dystonias). […] Otherwise, there may be evidence of a static structural lesion causing dystonia, as in the case of dystonic cerebral palsy following perinatal brain injury, or of progressive degeneration (e.g., PKAN, PLAN; formerly called „dystonia plus”).

• #5 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  Adult-onset idiopathic focal dystonia is the most common type of primary dystonia, and adult-onset idiopathic cervical dystonia (AOICD) is its most prevalent phenotype. […] Increasing evidence indicates that AOICD is a neurophysiological network disorder of GABAergic inhibition, causing a syndrome of dystonia, mood disturbance, and social cognitive dysfunction, with the superior colliculus playing a central role. […] Although classically considered a basal ganglia disorder, it is likely that superior colliculus dysfunction underlies the motor and non-motor symptoms. […] MRI evidence suggest that AOIFD is a network disorder affecting multiple distinct regions in the brain. […] Functionally, the superior colliculus (SC) likely plays a central role in disease mechanism, and this has been corroborated, particularly through utilisation of temporal discrimination.

• #6 Pathogenesis of dystonia: is it of cerebellar or basal ganglia origin? | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/89/5/488

  Dystonia was originally classified as a basal ganglia disease. It is now regarded as a network disorder including the cerebellum, but the exact pathogenesis being unknown. […] Recent animal studies showed physiologically tight disynaptic connections between the cerebellum and the striatum. […] We review clinical evidence in light of this new functional interaction between the cerebellum and basal ganglia, and put forward a hypothesis that dystonia is a basal ganglia disorder that can be induced by aberrant afferent inputs from the cerebellum. […] These findings indicate that aberrant inputs from the cerebellum to the basal ganglia may underlie the genesis of dystonia. […] The discovery of the functional disynaptic short-latency pathway from the cerebellum to the basal ganglia raises the possibility that cerebellar dysfunction could also cause dystonia by sending aberrant input to the striatum, where abnormal control of neural plasticity occurs as a result. […] Dystonia can be regarded as a disorder of aberrant input versus output plasticity or sensorimotor mismatch, which is clinically exemplified by sensory tricks or other sensory phenomena.

• #7 Dystonia: Symptoms, Causes, and Treatment Options

  https://brainfoundation.org.au/disorders/dystonia/

  Dystonia is a neurological movement disorder that causes muscles in the body to contract or spasm involuntarily. The causes of Dystonia are not yet fully understood, but it is thought that it may be caused by a chemical imbalance in a particular area of the brain called the basal ganglia where the messages to initiate muscle contractions are believed to originate. The basal ganglia are structures deep in the brain that are in part responsible for controlling movement. They regulate the numerous muscle contractions that are necessary to move the body. If this part of the brain is damaged in some way, the wrong muscles contract when we try to move. Or the muscles contract unnecessarily even when we are immobile, causing uncontrollable twitching, tremors and contractions. These spasms are known as dystonic movements.

• #8 Torticollis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1152543-overview

  As a neurodegenerative disease, torticollis, or idiopathic cervical dystonia, is believed to arise from basal ganglia circuit abnormalities stemming from selective vulnerability of these structures to an abnormal biochemical process that leads to neuronal dysfunction. […] The use of selective D2 ligands with single-photon emission computerized tomography (SPECT) scanning in 10 patients with torticollis has shown reduced D2-receptor binding in the basal ganglia. […] The implication is that underactivity occurs in the D2 dopamine receptors located in the indirect pallidal outflow pathway in both conditions. Such underactivity can be expected to cause disinhibited thalamocortical output and dystonic postures. […] This relative imbalance between direct (D1-related) and indirect (D2-related) pallidal outflow pathways explains the failure of levodopa to adequately improve torticollis and the transient improvement from traditional neuroleptic agents, which initially may reduce D1 activity and eventually both D1 and D2 activity in both pathways. […] Pramipexole is a dopamine agonist with selective, highly potent binding properties to D2 and D3 receptors. […] Further studies of receptor binding are needed to clarify the unknown process leading to the slow evolution and progression of torticollis.

• #9

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  The cerebellum was able to modulate striatal activity with a short latency via a disynaptic connection in mice. […] The occurrence of dystonic signs was thus dependent on the influence of both circuits which supports the hypothesis that dystonia results from a disruption of an integrated basal ganglia-cerebellar network rather than due to an isolated impairment of one of the structures. […] The close interaction of the cortico-basal ganglia and the cerebello-thalamic pathway was furthermore supported by the observation that patients with essential tremor and thalamic DBS had more beneficial DBS outcome when a specific cluster within the cerebello-thalamo-cortical tract was targeted. […] New evidence suggests that striosomal dysfunction could result in dysregulated dopamine release in the substantia nigra causing an imbalance between the direct and indirect pathway that is associated with impaired inhibition and the occurrence of dystonic movements. […] Recent evidence indicates that the cerebellum is likewise involved in the pathogenesis and that strong interactions between the basal ganglia and the cerebellum are present not only under physiological conditions but also in dystonia.

• #10 Dystonias: Practice Essentials, Classification, Common Types of Dystonias

  https://emedicine.medscape.com/article/312648-overview

  Cervical dystonia, or torticollis, is the most common focal dystonia. Intermittent spasms of the neck muscles or abnormal head movements occur because of contractions of the sternocleidomastoid, trapezius, and posterior cervical muscles. This effect results in a patterned, repetitive, and spasmodic movement that causes the head to twist (rotational torticollis), extend (retrocollis), flex (anterocollis), or tilt toward the shoulder (laterocollis). The patient may display more than 1 of these head movements simultaneously. […] Cervical dystonia is thought to result from involvement of the head of the caudate nucleus and thalamus, respectively. Disease of the thalamus and subthalamus, as well as derangement of hypothalamic function, also has been suspected. […] Because the basal ganglia play a role in maintaining normal head posture, the basal ganglia and the vestibulo-ocular reflex pathway have been implicated in the development of cervical dystonia. Disturbances of neurotransmitter systems also have been described in dystonias.

• #11 Advances in Our Understanding of Dystonia— Pathophysiology and Treatment Options – touchNEUROLOGY

  https://touchneurology.com/movement-disorders/journal-articles/advances-in-our-understanding-of-dystonia-pathophysiology-and-treatment-options/

  The primary neurophysiologic mechanisms considered to be important in dystonia pathogenesis include decreased cortical inhibition, increased cortical excitability, abnormal sensory processing, and maladaptive cortical plasticity. […] A central role for cholinergic dysfunction in dystonia pathogenesis is suggested by the observation that anticholinergic medications are the most effective pharmacologic agents in improving dystonia symptoms in primary dystonia patients. […] Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter and is also important in shaping plastic responses of the CNS to somatosensory and other stimuli, including the maintenance and plasticity of cortical receptive fields. […] The effectiveness of these classes of drugs is consistent with the findings discussed above of alterations in dopaminergic and cholinergic neurotransmission and reduced GABA-mediated inhibition in the dystonic CNS.

• #12 Cervical Dystonia | Portland Chiropractic Neurology

  https://portchiro.com/our-care/condition/cervical-dystonia/56/

  Cervical Dystonia is also known as Spasmodic Torticollis, it is described as a focal dystonia (or localized) that involves the neck and sometimes the shoulder. […] The etiology of Cervical Dystonia is unknown, but we now understand that it is associated with the Basal Ganglia and Parietal lobe of the Cortex. […] Cervical Dystonia can be inherited, as the DYT1 gene has been linked to individuals with this disorder.

• #13 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  Adult-onset idiopathic focal dystonia is the most common type of primary dystonia, and adult-onset idiopathic cervical dystonia (AOICD) is its most prevalent phenotype. […] Increasing evidence indicates that AOICD is a neurophysiological network disorder of GABAergic inhibition, causing a syndrome of dystonia, mood disturbance, and social cognitive dysfunction, with the superior colliculus playing a central role. […] Although classically considered a basal ganglia disorder, it is likely that superior colliculus dysfunction underlies the motor and non-motor symptoms. […] MRI evidence suggest that AOIFD is a network disorder affecting multiple distinct regions in the brain. […] Functionally, the superior colliculus (SC) likely plays a central role in disease mechanism, and this has been corroborated, particularly through utilisation of temporal discrimination.

• #14 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  AOIFDs could be considered a disorder due to disinhibition at the level of the SC. […] Animal studies have confirmed that SC disinhibition evokes dystonic posturing. […] The temporal discrimination threshold (TDT) is the shortest time interval at which two sequential stimuli are perceived as asynchronous. […] Patients and unaffected relatives with abnormal TDTs show reduced SC activity compared to controls, supporting the hypothesis that disrupted SC processing (loss of inhibition at the level of the SC) mediates abnormal temporal discrimination. […] The authors have previously described the importance of the collicularpulvinaramygdala network as a potential explanation for the spectrum of changes in AOIFD and CD.

• #15 The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia | Journal of Neuroscience

  https://www.jneurosci.org/content/33/47/18358

  Isolated focal dystonia is a neurological disorder that manifests as repetitive involuntary spasms and/or aberrant postures of the affected body part. Craniocervical dystonia involves muscles of the eye, jaw, larynx, or neck. The pathophysiology is unclear, and effective therapies are limited. One mechanism for increased muscle activity in craniocervical dystonia is loss of inhibition involving the trigeminal sensory nuclear complex (TSNC). […] In this review, we present a hypothetical extended brain network model that includes the TSNC in describing the pathophysiology of craniocervical dystonia. Our model suggests the TSNC may become hyperexcitable due to loss of tonic inhibition by functionally connected motor nuclei such as the motor cortex, basal ganglia, and cerebellum. […] We suggest that potentiation of the TSNC may also contribute to disordered sensorimotor control of face and neck muscles via ascending and cortical descending projections.

• #16

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  Another important concept in dystonia is the loss of inhibition on multiple levels of the central nervous system including cortex, basal ganglia, brainstem and spinal cord. […] This funneling or gating function of the basal ganglia is impaired in dystonia which results in an insufficient suppression of surrounding noisy activity, an excessive activation of cortical areas and subsequent co-contractions of muscle groups that otherwise should not be active. […] The inhibitory deficit in dystonia is probably associated not only with decreased GABA levels in the basal ganglia but also the cerebellum. […] A plethora of studies have found maladaptive plasticity in the striato-pallido-thalamo-cortical loop of dystonia patients using different non-invasive brain stimulation techniques. […] Recent evidence suggested similar maladaptive changes in the cerebellum.

• #17

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  Another important concept in dystonia is the loss of inhibition on multiple levels of the central nervous system including cortex, basal ganglia, brainstem and spinal cord. […] This funneling or gating function of the basal ganglia is impaired in dystonia which results in an insufficient suppression of surrounding noisy activity, an excessive activation of cortical areas and subsequent co-contractions of muscle groups that otherwise should not be active. […] The inhibitory deficit in dystonia is probably associated not only with decreased GABA levels in the basal ganglia but also the cerebellum. […] A plethora of studies have found maladaptive plasticity in the striato-pallido-thalamo-cortical loop of dystonia patients using different non-invasive brain stimulation techniques. […] Recent evidence suggested similar maladaptive changes in the cerebellum.

• #18

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  Another important concept in dystonia is the loss of inhibition on multiple levels of the central nervous system including cortex, basal ganglia, brainstem and spinal cord. […] This funneling or gating function of the basal ganglia is impaired in dystonia which results in an insufficient suppression of surrounding noisy activity, an excessive activation of cortical areas and subsequent co-contractions of muscle groups that otherwise should not be active. […] The inhibitory deficit in dystonia is probably associated not only with decreased GABA levels in the basal ganglia but also the cerebellum. […] A plethora of studies have found maladaptive plasticity in the striato-pallido-thalamo-cortical loop of dystonia patients using different non-invasive brain stimulation techniques. […] Recent evidence suggested similar maladaptive changes in the cerebellum.

• #19 The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia | Journal of Neuroscience

  https://www.jneurosci.org/content/33/47/18358

  Better understanding of the role of the TSNC within the extended neural network contributing to the pathophysiology of craniocervical dystonia may facilitate the development of new therapies such as noninvasive brain stimulation. […] Neurophysiological studies in people with dystonia have identified reduced inhibition in the CNS, in particular the sensorimotor cortex, basal ganglia, brainstem, spinal cord, and the cerebellum. […] Support for a role of the TSNC comes from clinical studies whereby trigeminal reflexes impacting on the control of cranial, facial and cervical muscles are aberrant in dystonia, consistent with decreased inhibitory modulation. […] We propose that this model should also include the TSNC when considering the pathophysiology underling craniocervical dystonia. […] The TSNC is elongated and extends from the midbrain to the upper cervical spinal cord. It primarily receives input from trigeminal nerve afferents but also receives sensory input from structures not supplied by the trigeminal nerve, in particular the neck muscles.

• #20 Frontiers Publishing Partnerships | Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia

  https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2022.10283/full

  The alleviating manoeuvres (AMs), classically referred to as “sensory tricks” are voluntary manoeuvres that temporarily improve dystonic postures. […] Different categories of AMs showed noteworthy differences in prevalence of use amongst CD patients, and in the relationship of frequency of use and efficacy to patient demographic and clinical characteristics. […] Beyond clinical characterization, a few groups have interrogated possible pathophysiological mechanisms underlying or related to AMs. […] Indeed, the presence of sensory trick as part of the behavioural phenomenology of dystonia has been acknowledged as a marker of abnormal sensorimotor integration in the pathophysiology of dystonia. […] Dystonia is conceptualized today as a network disorder, in which several structures implicated in sensory processing and sensorimotor integration, including the basal ganglia, cerebellum and the somatosensory cortical regions are dysfunctional.

• #21 Frontiers Publishing Partnerships | Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia

  https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2022.10283/full

  The alleviating manoeuvres (AMs), classically referred to as “sensory tricks” are voluntary manoeuvres that temporarily improve dystonic postures. […] Different categories of AMs showed noteworthy differences in prevalence of use amongst CD patients, and in the relationship of frequency of use and efficacy to patient demographic and clinical characteristics. […] Beyond clinical characterization, a few groups have interrogated possible pathophysiological mechanisms underlying or related to AMs. […] Indeed, the presence of sensory trick as part of the behavioural phenomenology of dystonia has been acknowledged as a marker of abnormal sensorimotor integration in the pathophysiology of dystonia. […] Dystonia is conceptualized today as a network disorder, in which several structures implicated in sensory processing and sensorimotor integration, including the basal ganglia, cerebellum and the somatosensory cortical regions are dysfunctional.

• #22 Cervical Dystonia | PM&R KnowledgeNow

  https://now.aapmr.org/cervical-dystonia/

  Cervical Dystonia (CD) is an adult-onset focal dystonia presenting with pain and involuntary cranio-cervical muscle activation leading to abnormal movements or postures (often twisting nature) affecting the head, neck, and or chin. […] The cause or causes of dystonia are not well established, and in many patients traditional neuroimaging studies are normal. Investigations have suggested potential causes including: […] Abnormalities in the brain sensorimotor systems as potential pathophysiologic mechanisms of dystonia. […] Damage to brain regions in the thalamus, brainstem, parietal lobe, cerebellum, and basal ganglia. […] Alterations in CNS inhibitory pathways. […] Disruptions in the various steps in dopamine synthesis or nigrostriatal dopamine neuron function ultimately affecting signaling in basal ganglia circuits. […] These findings suggest abnormalities in structure, integration processing, and loss of inhibition mediated by GABA levels. […] As noted above, the evidence implicating specific regions of the nervous system involved is lacking and disease progression and trajectory varies.

• #23 Frontiers Publishing Partnerships | Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia

  https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2022.10283/full

  One possible mechanism of action of the sensorimotor passive AM is related to the action on proprioceptors, and particularly on muscle spindles. […] There is evidence in the literature that proprioceptive dysfunction is involved in the pathophysiology of dystonia. […] The relaxation of dystonic muscles induced by P AMs may thus contribute to a modulation of afferent inputs from muscle spindles. […] This would lead to a modulation in the activity of γ-motor neurons, engaging a brainstem pathway that could ultimately reduce muscle spindle sensitivity. […] One of the possible mechanisms of action of botulinum neurotoxin, the first-line treatment for CD, is to block γ-motor neurons, causing reduced afferent activity of muscle spindles. […] We can speculate that P AMs produce their effect in a similar fashion.

• #24 Frontiers Publishing Partnerships | Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia

  https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2022.10283/full

  One possible mechanism of action of the sensorimotor passive AM is related to the action on proprioceptors, and particularly on muscle spindles. […] There is evidence in the literature that proprioceptive dysfunction is involved in the pathophysiology of dystonia. […] The relaxation of dystonic muscles induced by P AMs may thus contribute to a modulation of afferent inputs from muscle spindles. […] This would lead to a modulation in the activity of γ-motor neurons, engaging a brainstem pathway that could ultimately reduce muscle spindle sensitivity. […] One of the possible mechanisms of action of botulinum neurotoxin, the first-line treatment for CD, is to block γ-motor neurons, causing reduced afferent activity of muscle spindles. […] We can speculate that P AMs produce their effect in a similar fashion.

• #25

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  Another important concept in dystonia is the loss of inhibition on multiple levels of the central nervous system including cortex, basal ganglia, brainstem and spinal cord. […] This funneling or gating function of the basal ganglia is impaired in dystonia which results in an insufficient suppression of surrounding noisy activity, an excessive activation of cortical areas and subsequent co-contractions of muscle groups that otherwise should not be active. […] The inhibitory deficit in dystonia is probably associated not only with decreased GABA levels in the basal ganglia but also the cerebellum. […] A plethora of studies have found maladaptive plasticity in the striato-pallido-thalamo-cortical loop of dystonia patients using different non-invasive brain stimulation techniques. […] Recent evidence suggested similar maladaptive changes in the cerebellum.

• #26

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  Another important concept in dystonia is the loss of inhibition on multiple levels of the central nervous system including cortex, basal ganglia, brainstem and spinal cord. […] This funneling or gating function of the basal ganglia is impaired in dystonia which results in an insufficient suppression of surrounding noisy activity, an excessive activation of cortical areas and subsequent co-contractions of muscle groups that otherwise should not be active. […] The inhibitory deficit in dystonia is probably associated not only with decreased GABA levels in the basal ganglia but also the cerebellum. […] A plethora of studies have found maladaptive plasticity in the striato-pallido-thalamo-cortical loop of dystonia patients using different non-invasive brain stimulation techniques. […] Recent evidence suggested similar maladaptive changes in the cerebellum.

• #27 Impairment of sleep homeostasis in cervical dystonia patients | Scientific Reports

  https://www.nature.com/articles/s41598-022-10802-y

  Alterations in brain plasticity seem to play a role in the pathophysiology of cervical dystonia (CD). […] We hypothesized that an alteration in sleep homeostatic mechanisms may be involved in the pathogenesis of CD. […] Our data highlighted a pathophysiological relationship between SWA during sleep and CD and provided novel insight into the transient central plastic effect of BoNT. […] Alterations in cortical plasticity seem to play an important role in the pathophysiology of several types of dystonias. […] The lack of a substantial overnight decline in this slow activity in CD patients at Tpre-BoNT, reflecting an impaired synaptic downscaling process, might be linked to the abnormal cortical plasticity extensively described in dystonic patients. […] Remarkably, at BoNT maximal clinical efficacy (Tpost-BoNT), CD patients restored the physiological decrease of SWA throughout the night, associated to a considerable change in the SWA amount in the first part of the night.

• #28

  https://link.springer.com/article/10.1007/s00221-020-05833-8

  The study provided evidence of reversal of abnormally excessive motor cortex plasticity as a possible mechanism of action of GPi DBS for dystonia. […] The progressive time-course of improvement in dystonia symptoms after GPi DBS is well described and the finding of longitudinal changes in experimentally induced motor cortex plasticity suggests a potential mechanistic role. […] GPi DBS reduces ipsilateral excessive cortical activation in premotor and primary motor areas likely through enhanced thalamocortical inhibition. […] GPi DBS exerts potent inhibition of motor symptoms of dystonia and long-term changes in brainstem and spinal excitability, but seems ineffective in altering sensory endophenotypic defects, which supports their probable upstream role in dystonia pathogenesis. […] Dystonia pathophysiology as elucidated by neurophysiology shows wide ranging abnormalities some of which normalise after clinically effective GPi DBS. Excessive motor cortex plasticity and low frequency pallidal output may play a more direct role in generating dystonic movements. GPi DBS reduces the dystonic symptoms, in proportion to reductions in excessive motor cortex plasticity and low-frequency activity suggesting an important mechanistic role.

• #29

  https://link.springer.com/article/10.1007/s00221-020-05833-8

  The study provided evidence of reversal of abnormally excessive motor cortex plasticity as a possible mechanism of action of GPi DBS for dystonia. […] The progressive time-course of improvement in dystonia symptoms after GPi DBS is well described and the finding of longitudinal changes in experimentally induced motor cortex plasticity suggests a potential mechanistic role. […] GPi DBS reduces ipsilateral excessive cortical activation in premotor and primary motor areas likely through enhanced thalamocortical inhibition. […] GPi DBS exerts potent inhibition of motor symptoms of dystonia and long-term changes in brainstem and spinal excitability, but seems ineffective in altering sensory endophenotypic defects, which supports their probable upstream role in dystonia pathogenesis. […] Dystonia pathophysiology as elucidated by neurophysiology shows wide ranging abnormalities some of which normalise after clinically effective GPi DBS. Excessive motor cortex plasticity and low frequency pallidal output may play a more direct role in generating dystonic movements. GPi DBS reduces the dystonic symptoms, in proportion to reductions in excessive motor cortex plasticity and low-frequency activity suggesting an important mechanistic role.

• #30 Spasmodic torticollis – Wikipedia

  https://en.wikipedia.org/wiki/Spasmodic_torticollis

  The pathophysiology of spasmodic torticollis is still relatively unknown. Spasmodic torticollis is considered neurochemical in nature, and does not result in structural neurodegenerative changes. […] Studies have suggested that there is a functional imbalance in the striatal control of the globus pallidus, specifically the substantia nigra pars reticulata. The studies hypothesize the hyper activation of the cortical areas is due to reduced pallidal inhibition of the thalamus, leading to over activity of the medial and prefrontal cortical areas and under activity of the primary motor cortex during movement. […] It has also been suggested that the functional imbalance is due to an imbalance of neurotransmitters such as dopamine, acetylcholine, and gamma-aminobutyric acid. These neurotransmitters are secreted from the basal ganglia, traveling to muscle groups in the neck. An increase in neurotransmitters causes spasms to occur in the neck, resulting in spasmodic torticollis.

• #31 Spasmodic torticollis – Wikipedia

  https://en.wikipedia.org/wiki/Spasmodic_torticollis

  The pathophysiology of spasmodic torticollis is still relatively unknown. Spasmodic torticollis is considered neurochemical in nature, and does not result in structural neurodegenerative changes. […] Studies have suggested that there is a functional imbalance in the striatal control of the globus pallidus, specifically the substantia nigra pars reticulata. The studies hypothesize the hyper activation of the cortical areas is due to reduced pallidal inhibition of the thalamus, leading to over activity of the medial and prefrontal cortical areas and under activity of the primary motor cortex during movement. […] It has also been suggested that the functional imbalance is due to an imbalance of neurotransmitters such as dopamine, acetylcholine, and gamma-aminobutyric acid. These neurotransmitters are secreted from the basal ganglia, traveling to muscle groups in the neck. An increase in neurotransmitters causes spasms to occur in the neck, resulting in spasmodic torticollis.

• #32 Recovery From Cervical Dystonia With Topiramate | Putkonen | Journal of Medical Cases

  https://www.journalmc.org/index.php/jmc/article/view/2088/1606

  Primary cervical dystonia (CD), spasmodic torticollis, is the most common focal dystonia. […] CD is associated with reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] The pathophysiology of involuntary movements in dystonia and chorea, essential tremor, myoclonus and restless legs syndrome has been associated with a reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] Topiramate, a sulfamate-substituted monosaccharide, modulates both GABAergic and glutamatergic neurotransmission, as well as voltage-gated ion channels or intracellular signaling pathways. […] This case demonstrates that some patients recover from CD during treatment with topiramate, and remain asymptomatic for years. […] This is in accordance with the pharmacodynamic mechanisms of topiramate, the pathophysiological mechanisms of involuntary movements, and with the clinical evidence of topiramate in some other hyperkinetic movement disorders with similar pathophysiology. […] It would be important to conduct randomized controlled studies of topiramate in CD, and to define the subgroups who may benefit from it.

• #33 Advances in Our Understanding of Dystonia— Pathophysiology and Treatment Options – touchNEUROLOGY

  https://touchneurology.com/movement-disorders/journal-articles/advances-in-our-understanding-of-dystonia-pathophysiology-and-treatment-options/

  The primary neurophysiologic mechanisms considered to be important in dystonia pathogenesis include decreased cortical inhibition, increased cortical excitability, abnormal sensory processing, and maladaptive cortical plasticity. […] A central role for cholinergic dysfunction in dystonia pathogenesis is suggested by the observation that anticholinergic medications are the most effective pharmacologic agents in improving dystonia symptoms in primary dystonia patients. […] Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter and is also important in shaping plastic responses of the CNS to somatosensory and other stimuli, including the maintenance and plasticity of cortical receptive fields. […] The effectiveness of these classes of drugs is consistent with the findings discussed above of alterations in dopaminergic and cholinergic neurotransmission and reduced GABA-mediated inhibition in the dystonic CNS.

• #34 Torticollis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1152543-overview

  As a neurodegenerative disease, torticollis, or idiopathic cervical dystonia, is believed to arise from basal ganglia circuit abnormalities stemming from selective vulnerability of these structures to an abnormal biochemical process that leads to neuronal dysfunction. […] The use of selective D2 ligands with single-photon emission computerized tomography (SPECT) scanning in 10 patients with torticollis has shown reduced D2-receptor binding in the basal ganglia. […] The implication is that underactivity occurs in the D2 dopamine receptors located in the indirect pallidal outflow pathway in both conditions. Such underactivity can be expected to cause disinhibited thalamocortical output and dystonic postures. […] This relative imbalance between direct (D1-related) and indirect (D2-related) pallidal outflow pathways explains the failure of levodopa to adequately improve torticollis and the transient improvement from traditional neuroleptic agents, which initially may reduce D1 activity and eventually both D1 and D2 activity in both pathways. […] Pramipexole is a dopamine agonist with selective, highly potent binding properties to D2 and D3 receptors. […] Further studies of receptor binding are needed to clarify the unknown process leading to the slow evolution and progression of torticollis.

• #35 Torticollis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1152543-overview

  As a neurodegenerative disease, torticollis, or idiopathic cervical dystonia, is believed to arise from basal ganglia circuit abnormalities stemming from selective vulnerability of these structures to an abnormal biochemical process that leads to neuronal dysfunction. […] The use of selective D2 ligands with single-photon emission computerized tomography (SPECT) scanning in 10 patients with torticollis has shown reduced D2-receptor binding in the basal ganglia. […] The implication is that underactivity occurs in the D2 dopamine receptors located in the indirect pallidal outflow pathway in both conditions. Such underactivity can be expected to cause disinhibited thalamocortical output and dystonic postures. […] This relative imbalance between direct (D1-related) and indirect (D2-related) pallidal outflow pathways explains the failure of levodopa to adequately improve torticollis and the transient improvement from traditional neuroleptic agents, which initially may reduce D1 activity and eventually both D1 and D2 activity in both pathways. […] Pramipexole is a dopamine agonist with selective, highly potent binding properties to D2 and D3 receptors. […] Further studies of receptor binding are needed to clarify the unknown process leading to the slow evolution and progression of torticollis.

• #36 Pathogenesis of dystonia: is it of cerebellar or basal ganglia origin? | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/89/5/488

  Dystonia was originally classified as a basal ganglia disease. It is now regarded as a network disorder including the cerebellum, but the exact pathogenesis being unknown. […] Recent animal studies showed physiologically tight disynaptic connections between the cerebellum and the striatum. […] We review clinical evidence in light of this new functional interaction between the cerebellum and basal ganglia, and put forward a hypothesis that dystonia is a basal ganglia disorder that can be induced by aberrant afferent inputs from the cerebellum. […] These findings indicate that aberrant inputs from the cerebellum to the basal ganglia may underlie the genesis of dystonia. […] The discovery of the functional disynaptic short-latency pathway from the cerebellum to the basal ganglia raises the possibility that cerebellar dysfunction could also cause dystonia by sending aberrant input to the striatum, where abnormal control of neural plasticity occurs as a result. […] Dystonia can be regarded as a disorder of aberrant input versus output plasticity or sensorimotor mismatch, which is clinically exemplified by sensory tricks or other sensory phenomena.

• #37 Pathogenesis of dystonia: is it of cerebellar or basal ganglia origin? | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/89/5/488

  Dystonia was originally classified as a basal ganglia disease. It is now regarded as a network disorder including the cerebellum, but the exact pathogenesis being unknown. […] Recent animal studies showed physiologically tight disynaptic connections between the cerebellum and the striatum. […] We review clinical evidence in light of this new functional interaction between the cerebellum and basal ganglia, and put forward a hypothesis that dystonia is a basal ganglia disorder that can be induced by aberrant afferent inputs from the cerebellum. […] These findings indicate that aberrant inputs from the cerebellum to the basal ganglia may underlie the genesis of dystonia. […] The discovery of the functional disynaptic short-latency pathway from the cerebellum to the basal ganglia raises the possibility that cerebellar dysfunction could also cause dystonia by sending aberrant input to the striatum, where abnormal control of neural plasticity occurs as a result. […] Dystonia can be regarded as a disorder of aberrant input versus output plasticity or sensorimotor mismatch, which is clinically exemplified by sensory tricks or other sensory phenomena.

• #38

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  The cerebellum was able to modulate striatal activity with a short latency via a disynaptic connection in mice. […] The occurrence of dystonic signs was thus dependent on the influence of both circuits which supports the hypothesis that dystonia results from a disruption of an integrated basal ganglia-cerebellar network rather than due to an isolated impairment of one of the structures. […] The close interaction of the cortico-basal ganglia and the cerebello-thalamic pathway was furthermore supported by the observation that patients with essential tremor and thalamic DBS had more beneficial DBS outcome when a specific cluster within the cerebello-thalamo-cortical tract was targeted. […] New evidence suggests that striosomal dysfunction could result in dysregulated dopamine release in the substantia nigra causing an imbalance between the direct and indirect pathway that is associated with impaired inhibition and the occurrence of dystonic movements. […] Recent evidence indicates that the cerebellum is likewise involved in the pathogenesis and that strong interactions between the basal ganglia and the cerebellum are present not only under physiological conditions but also in dystonia.

• #39 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  Adult-onset idiopathic focal dystonia is the most common type of primary dystonia, and adult-onset idiopathic cervical dystonia (AOICD) is its most prevalent phenotype. […] Increasing evidence indicates that AOICD is a neurophysiological network disorder of GABAergic inhibition, causing a syndrome of dystonia, mood disturbance, and social cognitive dysfunction, with the superior colliculus playing a central role. […] Although classically considered a basal ganglia disorder, it is likely that superior colliculus dysfunction underlies the motor and non-motor symptoms. […] MRI evidence suggest that AOIFD is a network disorder affecting multiple distinct regions in the brain. […] Functionally, the superior colliculus (SC) likely plays a central role in disease mechanism, and this has been corroborated, particularly through utilisation of temporal discrimination.

• #40 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  AOIFDs could be considered a disorder due to disinhibition at the level of the SC. […] Animal studies have confirmed that SC disinhibition evokes dystonic posturing. […] The temporal discrimination threshold (TDT) is the shortest time interval at which two sequential stimuli are perceived as asynchronous. […] Patients and unaffected relatives with abnormal TDTs show reduced SC activity compared to controls, supporting the hypothesis that disrupted SC processing (loss of inhibition at the level of the SC) mediates abnormal temporal discrimination. […] The authors have previously described the importance of the collicularpulvinaramygdala network as a potential explanation for the spectrum of changes in AOIFD and CD.

• #41 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  AOIFDs could be considered a disorder due to disinhibition at the level of the SC. […] Animal studies have confirmed that SC disinhibition evokes dystonic posturing. […] The temporal discrimination threshold (TDT) is the shortest time interval at which two sequential stimuli are perceived as asynchronous. […] Patients and unaffected relatives with abnormal TDTs show reduced SC activity compared to controls, supporting the hypothesis that disrupted SC processing (loss of inhibition at the level of the SC) mediates abnormal temporal discrimination. […] The authors have previously described the importance of the collicularpulvinaramygdala network as a potential explanation for the spectrum of changes in AOIFD and CD.

• #42 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  AOIFDs could be considered a disorder due to disinhibition at the level of the SC. […] Animal studies have confirmed that SC disinhibition evokes dystonic posturing. […] The temporal discrimination threshold (TDT) is the shortest time interval at which two sequential stimuli are perceived as asynchronous. […] Patients and unaffected relatives with abnormal TDTs show reduced SC activity compared to controls, supporting the hypothesis that disrupted SC processing (loss of inhibition at the level of the SC) mediates abnormal temporal discrimination. […] The authors have previously described the importance of the collicularpulvinaramygdala network as a potential explanation for the spectrum of changes in AOIFD and CD.

• #43 Role of supplementary motor area in cervical dystonia and sensory tricks | Scientific Reports

  https://www.nature.com/articles/s41598-022-25316-w

  Sensory trick is a characteristic feature of cervical dystonia (CD), where a light touch on the area adjacent to the dystonia temporarily improves symptoms. […] The supplementary motor area (SMA) may dynamically interact with the sensorimotor network and other brain regions during sensory tricks in patients with CD. […] Our study results showed a crucial role of SMA in sensorimotor processing during sensory trick performance and imagination and suggest the IPS as a novel potential therapeutic target for brain modulation. […] Despite their high prevalence, the mechanism has remained elusive. […] Evidence from neurophysiology and neuroimaging studies as well as clinical observation suggest the role of the SMA in sensory tricks. […] Our current fMRI study results showed direct evidence that SMA plays a crucial role during sensory tricks in CD.

• #44 Role of supplementary motor area in cervical dystonia and sensory tricks | Scientific Reports

  https://www.nature.com/articles/s41598-022-25316-w

  Sensory trick is a characteristic feature of cervical dystonia (CD), where a light touch on the area adjacent to the dystonia temporarily improves symptoms. […] The supplementary motor area (SMA) may dynamically interact with the sensorimotor network and other brain regions during sensory tricks in patients with CD. […] Our study results showed a crucial role of SMA in sensorimotor processing during sensory trick performance and imagination and suggest the IPS as a novel potential therapeutic target for brain modulation. […] Despite their high prevalence, the mechanism has remained elusive. […] Evidence from neurophysiology and neuroimaging studies as well as clinical observation suggest the role of the SMA in sensory tricks. […] Our current fMRI study results showed direct evidence that SMA plays a crucial role during sensory tricks in CD.

• #45 Role of supplementary motor area in cervical dystonia and sensory tricks | Scientific Reports

  https://www.nature.com/articles/s41598-022-25316-w

  Our results showed that SMA connectivity with brain regions of sensory integration was different at rest between HC and patients. […] The most compelling finding from our study is how connectivity changes between the SMA and posterior parietal cortex during sensory tricks. […] Our result indicates that SMA may play a key role in sensory tricks in CD by partially correcting aberrant sensorimotor processing. […] Our study indicated that the prefronto-cerebellar circuit might work differently in CD patients compared to HC in response to motor, imaginary, and light touch. […] Overall, our results clearly showed the differences in SMA connectivity in HC and CD patients during sensory trick performance and imagination.

• #46 Role of supplementary motor area in cervical dystonia and sensory tricks | Scientific Reports

  https://www.nature.com/articles/s41598-022-25316-w

  Our results showed that SMA connectivity with brain regions of sensory integration was different at rest between HC and patients. […] The most compelling finding from our study is how connectivity changes between the SMA and posterior parietal cortex during sensory tricks. […] Our result indicates that SMA may play a key role in sensory tricks in CD by partially correcting aberrant sensorimotor processing. […] Our study indicated that the prefronto-cerebellar circuit might work differently in CD patients compared to HC in response to motor, imaginary, and light touch. […] Overall, our results clearly showed the differences in SMA connectivity in HC and CD patients during sensory trick performance and imagination.

• #47

  https://link.springer.com/article/10.1007/s00702-021-02299-y

  Striosomal dysfunction has been implicated in hyperkinetic movement disorders including dystonia. […] The etiology of dystonias is heterogeneous and includes acquired, genetic and sporadic forms. […] The acquired forms result from injuries of critical neuronal structures, whereas genetic forms are associated with pathogenic mutations in dystonia-causing genes. […] Discoveries in these two etiologies have largely supported the understanding of the underlying functional neuroanatomy and pathophysiology of dystonias. […] The most common clinical constellation in dystonia, however, is the absence of neuronal lesions and disease-causing mutations. […] In these sporadic cases, complex gene-environment interactions are discussed to cause the disease. […] One major challenge is that such abnormalities can be observed in other brain disorders as well and may thus not be causal but rather a consequence of dystonic muscle activity.

• #48 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Dystonia is a syndrome of sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal posturing. Cervical dystonia (CD) is a form of dystonia that involves neck muscles. […] Patients with CD are classified according to aetiology into two groups: primary CD (idiopathic–may be genetic or sporadic) or secondary CD (symptomatic). Patients with primary CD have no evidence by history, physical examination or laboratory studies (except primary dystonia gene) of any secondary cause for the dystonic symptoms. CD is a part of either generalised or focal dystonic syndrome which may have a genetic basis, with an identifiable genetic association. Secondary or symptomatic CD may be caused by central or peripheral trauma, exposure to dopamine receptor antagonists (tardive), neurodegenerative disease, and other conditions associated with abnormal functioning of the basal ganglia. In the majority of patients with CD, the aetiology is not identifiable and the disorder is often classified as primary.

• #49 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Dystonia is a syndrome of sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal posturing. Cervical dystonia (CD) is a form of dystonia that involves neck muscles. […] Patients with CD are classified according to aetiology into two groups: primary CD (idiopathic–may be genetic or sporadic) or secondary CD (symptomatic). Patients with primary CD have no evidence by history, physical examination or laboratory studies (except primary dystonia gene) of any secondary cause for the dystonic symptoms. CD is a part of either generalised or focal dystonic syndrome which may have a genetic basis, with an identifiable genetic association. Secondary or symptomatic CD may be caused by central or peripheral trauma, exposure to dopamine receptor antagonists (tardive), neurodegenerative disease, and other conditions associated with abnormal functioning of the basal ganglia. In the majority of patients with CD, the aetiology is not identifiable and the disorder is often classified as primary.

• #50 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Dystonia is a syndrome of sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal posturing. Cervical dystonia (CD) is a form of dystonia that involves neck muscles. […] Patients with CD are classified according to aetiology into two groups: primary CD (idiopathic–may be genetic or sporadic) or secondary CD (symptomatic). Patients with primary CD have no evidence by history, physical examination or laboratory studies (except primary dystonia gene) of any secondary cause for the dystonic symptoms. CD is a part of either generalised or focal dystonic syndrome which may have a genetic basis, with an identifiable genetic association. Secondary or symptomatic CD may be caused by central or peripheral trauma, exposure to dopamine receptor antagonists (tardive), neurodegenerative disease, and other conditions associated with abnormal functioning of the basal ganglia. In the majority of patients with CD, the aetiology is not identifiable and the disorder is often classified as primary.

• #51 Evaluation of outcome of different neurosurgical modalities in management of cervical dystonia | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00493-7

  Cervical dystonia (CD) is the most common adult-onset focal dystonia, characterized by involuntary, intermittent, or sustained muscle contractions causing abnormal neck postures. […] The definitive mechanism underlying the pathogenesis of CD is unclear and a unifying theory is lacking; however, several factors including genetic and environmental factors such as trauma have been implicated. […] CD is part of either generalized or focal dystonic syndromes which may have a genetic basis, with an identifiable genetic association. Secondary CD may result from central or peripheral trauma, neurodegenerative disease, exposure to dopamine receptor antagonists (tardive dystonia), and any other conditions associated with abnormal functioning of the basal ganglia. […] The aim of management is not the cure of the disease, but to ameliorate symptoms, social and functional disability, and to decrease the incidence of complications encountered in the cervical spine such as cervical spondylosis, disc herniation, cervical radiculopathy, cervical myelopathy, vertebral subluxation, fractures, muscle contractures, and fixed bony deformity.

• #52 Dystonia: Symptoms, Causes, and Treatment Options

  https://brainfoundation.org.au/disorders/dystonia/

  A number of different genes on different chromosomes have now been identified as being linked with different types of dystonia, but researchers dont yet know exactly how a particular gene causes dystonia. The DYT1 gene on chromosome 9, which is related to early-onset generalised dystonia, was only located in 1997. One benefit of finding this single mutation for familial dystonia is that genetic counselling and testing will in future be available for appropriate individuals. […] As with all genetic research, the next step will be to work out what the function of the gene is, and how it causes dystonia.

• #53

  https://journals.lww.com/co-neurology/fulltext/2014/08000/Dystonia___an_update_on_phenomenology,.14.aspx?generateEpub=Article%7Cco-neurology:2014:08000:00014%7C10.1097/wco.0000000000000114%7C

  Based on phenomenology, a new consensus update on the definition, phenomenology and classification of dystonia and a syndromic approach to guide diagnosis have been proposed. […] The recently discovered genes ANO3, GNAL and CIZ1 appear not to be a common cause of adult-onset cervical dystonia. […] The identification of new genes will facilitate better elucidation of pathogenetic mechanisms and possible corrective therapies.

• #54 Cervical Dystonia – Samir P. Macwan, MD

  https://socalmusclenerve.com/cervical-dystonia/

  Cervical dystonia is a neurological movement disorder that causes the muscles in your neck to contract (tighten) involuntarily. […] Cervical dystonia is classified as an isolated dystonia if there are no other associated abnormal findings, such as spasticity, Parkinsonism or ataxia. Most isolated cervical dystonia had no identifiable underlying causes. However, in some cases, cervical dystonia can arise from another underlying cause and be considered secondary (occurring as consequence of another disorder or condition). […] Cervical dystonia is associated with changes (mutations) in several genes (GNAL, THAP1, CIZ1, ANO3 genes) and several possible environmental factors. […] Cervical dystonia is a neurological disorder. […] Botulinum toxin works by preventing the nerve from releasing a messenger, called acetylcholine, that tells the muscle to contract. […] Deep brain stimulation surgery (DBS) is effective for cervical dystonia and may be appropriate for patients who lose their response to botulinum toxin, or have a form of cervical dystonia that is difficult to treat with the injections, in particular anterocollis.

• #55 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Dystonia is a syndrome of sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal posturing. Cervical dystonia (CD) is a form of dystonia that involves neck muscles. […] Patients with CD are classified according to aetiology into two groups: primary CD (idiopathic–may be genetic or sporadic) or secondary CD (symptomatic). Patients with primary CD have no evidence by history, physical examination or laboratory studies (except primary dystonia gene) of any secondary cause for the dystonic symptoms. CD is a part of either generalised or focal dystonic syndrome which may have a genetic basis, with an identifiable genetic association. Secondary or symptomatic CD may be caused by central or peripheral trauma, exposure to dopamine receptor antagonists (tardive), neurodegenerative disease, and other conditions associated with abnormal functioning of the basal ganglia. In the majority of patients with CD, the aetiology is not identifiable and the disorder is often classified as primary.

• #56 Evaluation of outcome of different neurosurgical modalities in management of cervical dystonia | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00493-7

  Cervical dystonia (CD) is the most common adult-onset focal dystonia, characterized by involuntary, intermittent, or sustained muscle contractions causing abnormal neck postures. […] The definitive mechanism underlying the pathogenesis of CD is unclear and a unifying theory is lacking; however, several factors including genetic and environmental factors such as trauma have been implicated. […] CD is part of either generalized or focal dystonic syndromes which may have a genetic basis, with an identifiable genetic association. Secondary CD may result from central or peripheral trauma, neurodegenerative disease, exposure to dopamine receptor antagonists (tardive dystonia), and any other conditions associated with abnormal functioning of the basal ganglia. […] The aim of management is not the cure of the disease, but to ameliorate symptoms, social and functional disability, and to decrease the incidence of complications encountered in the cervical spine such as cervical spondylosis, disc herniation, cervical radiculopathy, cervical myelopathy, vertebral subluxation, fractures, muscle contractures, and fixed bony deformity.

• #57 Cervical Dystonia – Brain, Spinal Cord, and Nerve Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/movement-disorders/cervical-dystonia

  Cervical dystonia is characterized by long-lasting (chronic sustained) involuntary contractions or periodic, intermittent spasms of the neck muscles, causing the neck to turn in different ways. […] The cause of cervical dystonia is usually unknown. […] Usually, the cause is unknown, but in some people, spasmodic torticollis is caused by a genetic mutation. Stress and emotional problems may make spasmodic torticollis worse. […] Cervical dystonia can be present at birth, occur later, caused by various neurologic disorders, or result from the use of medications that block dopamine (such as haloperidol and other antipsychotic medications). […] In about 70% of people with cervical dystonia, injections of botulinum toxin into the affected muscles can reduce painful spasms for 1 to 4 months and allow the head to return to a more normal position.

• #58 Cervical Dystonia: Symptoms, Causes, Treatment

  https://www.verywellhealth.com/cervical-dystonia-7371429

  Cervical dystonia is a neurological condition affecting approximately 60,000 people in the United States. […] The exact cause of cervical dystonia is unknown. However, certain risk factors can increase your chances of developing this condition. Cervical dystonia is more common among 40- to 60-year-old people assigned female at birth and people with a family history of the condition. […] Cervical dystonia can also be a secondary condition caused by other medical problems, such as stroke, Parkinson’s disease, traumatic brain injury, previous neck injury, and conditions that affect the basal ganglia (located at the base of the brain). […] Deep brain stimulation (DBS) is a surgical procedure that can treat cervical dystonia. It involves placing electrodes into brain structures on both sides of the brain.

• #59 Dystonia: Symptoms, Causes, and Treatment Options

  https://brainfoundation.org.au/disorders/dystonia/

  Some patients may have suffered from an illness or injury which has damaged the basal ganglia, but in the majority of cases the underlying cause of the condition is unknown. If no cause can be pinpointed, the dystonia is said to be idiopathic. […] The link between trauma and dystonia is not yet fully understood. It appears from published studies that persons who are carriers of a gene for dystonia may be more likely to have trauma as a triggering factor for the development of dystonia. […] A number of uncommon toxins are capable of causing brain damage centred in the motor control region known as the basal ganglia. Dystonia may be one prominent feature experienced by people with these exposures, but it is extremely uncommon for isolated dystonia to be seen in such patients. […] The role of environmental factors causing or contributing to dystonia remains uncertain. It is not clear why some individuals inheriting a special gene develop a severe form of dystonia while many others who have inherited the same gene either never develop the problem or only demonstrate a very mild form (this is what is meant by variable penetrance in genetics parlance).

• #60 Impairment of sleep homeostasis in cervical dystonia patients | Scientific Reports

  https://www.nature.com/articles/s41598-022-10802-y

  Alterations in brain plasticity seem to play a role in the pathophysiology of cervical dystonia (CD). […] We hypothesized that an alteration in sleep homeostatic mechanisms may be involved in the pathogenesis of CD. […] Our data highlighted a pathophysiological relationship between SWA during sleep and CD and provided novel insight into the transient central plastic effect of BoNT. […] Alterations in cortical plasticity seem to play an important role in the pathophysiology of several types of dystonias. […] The lack of a substantial overnight decline in this slow activity in CD patients at Tpre-BoNT, reflecting an impaired synaptic downscaling process, might be linked to the abnormal cortical plasticity extensively described in dystonic patients. […] Remarkably, at BoNT maximal clinical efficacy (Tpost-BoNT), CD patients restored the physiological decrease of SWA throughout the night, associated to a considerable change in the SWA amount in the first part of the night.

• #61 Impairment of sleep homeostasis in cervical dystonia patients | Scientific Reports

  https://www.nature.com/articles/s41598-022-10802-y

  Alterations in brain plasticity seem to play a role in the pathophysiology of cervical dystonia (CD). […] We hypothesized that an alteration in sleep homeostatic mechanisms may be involved in the pathogenesis of CD. […] Our data highlighted a pathophysiological relationship between SWA during sleep and CD and provided novel insight into the transient central plastic effect of BoNT. […] Alterations in cortical plasticity seem to play an important role in the pathophysiology of several types of dystonias. […] The lack of a substantial overnight decline in this slow activity in CD patients at Tpre-BoNT, reflecting an impaired synaptic downscaling process, might be linked to the abnormal cortical plasticity extensively described in dystonic patients. […] Remarkably, at BoNT maximal clinical efficacy (Tpost-BoNT), CD patients restored the physiological decrease of SWA throughout the night, associated to a considerable change in the SWA amount in the first part of the night.

• #62 Impairment of sleep homeostasis in cervical dystonia patients | Scientific Reports

  https://www.nature.com/articles/s41598-022-10802-y

  Alterations in brain plasticity seem to play a role in the pathophysiology of cervical dystonia (CD). […] We hypothesized that an alteration in sleep homeostatic mechanisms may be involved in the pathogenesis of CD. […] Our data highlighted a pathophysiological relationship between SWA during sleep and CD and provided novel insight into the transient central plastic effect of BoNT. […] Alterations in cortical plasticity seem to play an important role in the pathophysiology of several types of dystonias. […] The lack of a substantial overnight decline in this slow activity in CD patients at Tpre-BoNT, reflecting an impaired synaptic downscaling process, might be linked to the abnormal cortical plasticity extensively described in dystonic patients. […] Remarkably, at BoNT maximal clinical efficacy (Tpost-BoNT), CD patients restored the physiological decrease of SWA throughout the night, associated to a considerable change in the SWA amount in the first part of the night.

• #63 Impairment of sleep homeostasis in cervical dystonia patients | Scientific Reports

  https://www.nature.com/articles/s41598-022-10802-y

  This corroborates the pathogenic role of sleep homeostasis impairment in the appearance of CD and the hypothesis that BoNT might exert its clinical benefit through CNS-mediated mechanisms. […] Taken together, all these findings provide novel insight into the transiently central plastic effect of BoNT and the consecutive reorganization of the brain. […] In conclusion, we highlighted a pathophysiological relationship between sleep and CD and provided further evidence of a central effect of BoNT.

• #64 A Metabolomic Study of Cervical Dystonia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.08.30.274126.full

  Pathway analysis revealed 9 biological processes to be significantly associated at p<0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism. [...] An interesting metabolite that was identified as potentially abnormal in CD was the oxidized lipid 2-hydroxydecanoate. [...] Among the biological pathways that were significantly associated with CD, five were related to carbohydrate metabolism, suggesting a potential link with energy production. Three pathways were related to lipid metabolism, which produces prostaglandins and other metabolites known to mediate inflammatory responses. [...] Thus, the immune link suggested by our metabolomics findings may be worthy of further investigation. [...] This report describes the first large-scale metabolomics study for CD, the most common form of the idiopathic adult-onset dystonia. [...] These results provide novel insights into the biological basis for CD.

• #65 A Metabolomic Study of Cervical Dystonia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.08.30.274126.full

  Pathway analysis revealed 9 biological processes to be significantly associated at p<0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism. [...] An interesting metabolite that was identified as potentially abnormal in CD was the oxidized lipid 2-hydroxydecanoate. [...] Among the biological pathways that were significantly associated with CD, five were related to carbohydrate metabolism, suggesting a potential link with energy production. Three pathways were related to lipid metabolism, which produces prostaglandins and other metabolites known to mediate inflammatory responses. [...] Thus, the immune link suggested by our metabolomics findings may be worthy of further investigation. [...] This report describes the first large-scale metabolomics study for CD, the most common form of the idiopathic adult-onset dystonia. [...] These results provide novel insights into the biological basis for CD.

• #66 A Metabolomic Study of Cervical Dystonia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.08.30.274126.full

  Pathway analysis revealed 9 biological processes to be significantly associated at p<0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism. [...] An interesting metabolite that was identified as potentially abnormal in CD was the oxidized lipid 2-hydroxydecanoate. [...] Among the biological pathways that were significantly associated with CD, five were related to carbohydrate metabolism, suggesting a potential link with energy production. Three pathways were related to lipid metabolism, which produces prostaglandins and other metabolites known to mediate inflammatory responses. [...] Thus, the immune link suggested by our metabolomics findings may be worthy of further investigation. [...] This report describes the first large-scale metabolomics study for CD, the most common form of the idiopathic adult-onset dystonia. [...] These results provide novel insights into the biological basis for CD.

• #67 Idiopathic cervical dystonia – does autoimmunity play a hand? – MDS Abstracts

  https://www.mdsabstracts.org/abstract/idiopathic-cervical-dystonia-does-autoimmunity-play-a-hand/

  Idiopathic cervical dystonia does autoimmunity play a hand? […] Autoimmunity may play a role in CD pathogenesis.

• #68 A Metabolomic Study of Cervical Dystonia | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.08.30.274126.full

  Pathway analysis revealed 9 biological processes to be significantly associated at p<0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism. [...] An interesting metabolite that was identified as potentially abnormal in CD was the oxidized lipid 2-hydroxydecanoate. [...] Among the biological pathways that were significantly associated with CD, five were related to carbohydrate metabolism, suggesting a potential link with energy production. Three pathways were related to lipid metabolism, which produces prostaglandins and other metabolites known to mediate inflammatory responses. [...] Thus, the immune link suggested by our metabolomics findings may be worthy of further investigation. [...] This report describes the first large-scale metabolomics study for CD, the most common form of the idiopathic adult-onset dystonia. [...] These results provide novel insights into the biological basis for CD.

• #69 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Unless the aetiological investigation reveals a specific therapeutic intervention, therapy for CD is symptomatic. It includes supportive therapy and counselling, physical therapy, pharmacotherapy, chemodenervation [botulinum toxin (BTX), phenol, alcohol], and central and peripheral surgical therapy. The most widely used and accepted therapy for CD is local intramuscular injections of BTX-type A. Currently, both BTX type A and type B are commercially available, and type F has undergone testing. Pharmacotherapy, including anticholinergics, dopaminergic depleting and blocking agents, and other muscle relaxants can be used alone or in combination with other therapeutic interventions. Surgery is usually reserved for patients with CD in whom other forms of treatment have failed.

• #70 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Unless the aetiological investigation reveals a specific therapeutic intervention, therapy for CD is symptomatic. It includes supportive therapy and counselling, physical therapy, pharmacotherapy, chemodenervation [botulinum toxin (BTX), phenol, alcohol], and central and peripheral surgical therapy. The most widely used and accepted therapy for CD is local intramuscular injections of BTX-type A. Currently, both BTX type A and type B are commercially available, and type F has undergone testing. Pharmacotherapy, including anticholinergics, dopaminergic depleting and blocking agents, and other muscle relaxants can be used alone or in combination with other therapeutic interventions. Surgery is usually reserved for patients with CD in whom other forms of treatment have failed.

• #71

  https://practicalneurology.com/articles/2020-oct/movement-disorders-moment-treatment-approaches-to-cervical-dystonia

  Mechanism of Action. Botulinum toxin acts on CD by reducing excessive tone through acetylcholine inhibition to alleviate painful muscle spasms. Muscle atrophy is observed after 2 weeks with subsequent recovery of approximately 80% of muscle mass over the next 12 to 14 weeks is thought to contribute to decompression of nerves, increased tissue perfusion, and improved muscle metabolism. Pain relief, however, is not associated with dose, suggesting pain improvement is not related only to muscle weakening. A central mechanism of pain relief is also hypothesized considering that botulinum toxin is associated with partial normalization of brain activity and connectivity within the basal ganglia and the sensorimotor network in patients with CD. […] The mechanism of DBS in CD treatment is unknown. In a single case report, pain improvement with DBS of the globus pallidus internus (GPi) could be temporally dissociated from motor and postural improvement, suggesting that dysfunction of motor and somatosensory circuits in CD is not always in parallel. […] Further research is needed to compare efficacy of available botulinum neurotoxins on pain reduction and long-term benefits.

• #72

  https://practicalneurology.com/articles/2020-oct/movement-disorders-moment-treatment-approaches-to-cervical-dystonia

  Mechanism of Action. Botulinum toxin acts on CD by reducing excessive tone through acetylcholine inhibition to alleviate painful muscle spasms. Muscle atrophy is observed after 2 weeks with subsequent recovery of approximately 80% of muscle mass over the next 12 to 14 weeks is thought to contribute to decompression of nerves, increased tissue perfusion, and improved muscle metabolism. Pain relief, however, is not associated with dose, suggesting pain improvement is not related only to muscle weakening. A central mechanism of pain relief is also hypothesized considering that botulinum toxin is associated with partial normalization of brain activity and connectivity within the basal ganglia and the sensorimotor network in patients with CD. […] The mechanism of DBS in CD treatment is unknown. In a single case report, pain improvement with DBS of the globus pallidus internus (GPi) could be temporally dissociated from motor and postural improvement, suggesting that dysfunction of motor and somatosensory circuits in CD is not always in parallel. […] Further research is needed to compare efficacy of available botulinum neurotoxins on pain reduction and long-term benefits.

• #73 How MYOBLOC Helps Treat Cervical Dystonia

  https://www.myoblochcp.com/for-cervical-dystonia

  MYOBLOC is the first FDA-approved neurotoxin for the treatment of cervical dystonia (abnormal head position/neck pain) and a proven botulinum toxin B. Explore the evidence behind its strong legacy that extends back to 2000. […] MYOBLOC has a distinct mechanism of action. […] For cervical dystonia, blocking ACh release inhibits muscle contraction and allows the injected muscle to assume a more normal tone. […] Significant clinical efficacy in both Toxin A-responsive and -resistant cervical dystonia. […] MYOBLOC provided significant pain reduction for both Toxin A-responsive and Toxin A-resistant patients at Week 4. […] MYOBLOC has demonstrated tolerability.

• #74 How MYOBLOC Helps Treat Cervical Dystonia

  https://www.myoblochcp.com/for-cervical-dystonia

  MYOBLOC is the first FDA-approved neurotoxin for the treatment of cervical dystonia (abnormal head position/neck pain) and a proven botulinum toxin B. Explore the evidence behind its strong legacy that extends back to 2000. […] MYOBLOC has a distinct mechanism of action. […] For cervical dystonia, blocking ACh release inhibits muscle contraction and allows the injected muscle to assume a more normal tone. […] Significant clinical efficacy in both Toxin A-responsive and -resistant cervical dystonia. […] MYOBLOC provided significant pain reduction for both Toxin A-responsive and Toxin A-resistant patients at Week 4. […] MYOBLOC has demonstrated tolerability.

• #75 The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia: Lessons from Magnetoencephalography | Tremor and Other Hyperkinetic Movements

  https://tremorjournal.org/articles/10.5334/tohm.348

  Pharmacological management of cervical dystonia (CD) is considered to be symptomatic in effect, rather than targeting the underlying pathophysiology of the disease. […] More recently, studies have indicated that reduced intracortical inhibition and distorted somatotopic cortical representation in the somatosensory cortex play a critical role in the pathogenesis of dystonia. […] Botulinum toxin is believed to have a symptomatic benefit in dystonia with no effect on the underlying pathophysiology. […] These results may indicate a central mechanism to the clinical benefit. In addition, the presence of increased interhemispheric coherence, apart from intrahemispheric coherence, perhaps points toward the importance of global and local networks in the pathophysiology of dystonia. […] This may indicate the underlying pathophysiology of CD.

• #76 The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia: Lessons from Magnetoencephalography | Tremor and Other Hyperkinetic Movements

  https://tremorjournal.org/articles/10.5334/tohm.348

  Pharmacological management of cervical dystonia (CD) is considered to be symptomatic in effect, rather than targeting the underlying pathophysiology of the disease. […] More recently, studies have indicated that reduced intracortical inhibition and distorted somatotopic cortical representation in the somatosensory cortex play a critical role in the pathogenesis of dystonia. […] Botulinum toxin is believed to have a symptomatic benefit in dystonia with no effect on the underlying pathophysiology. […] These results may indicate a central mechanism to the clinical benefit. In addition, the presence of increased interhemispheric coherence, apart from intrahemispheric coherence, perhaps points toward the importance of global and local networks in the pathophysiology of dystonia. […] This may indicate the underlying pathophysiology of CD.

• #77

  https://practicalneurology.com/articles/2020-oct/movement-disorders-moment-treatment-approaches-to-cervical-dystonia

  Mechanism of Action. Botulinum toxin acts on CD by reducing excessive tone through acetylcholine inhibition to alleviate painful muscle spasms. Muscle atrophy is observed after 2 weeks with subsequent recovery of approximately 80% of muscle mass over the next 12 to 14 weeks is thought to contribute to decompression of nerves, increased tissue perfusion, and improved muscle metabolism. Pain relief, however, is not associated with dose, suggesting pain improvement is not related only to muscle weakening. A central mechanism of pain relief is also hypothesized considering that botulinum toxin is associated with partial normalization of brain activity and connectivity within the basal ganglia and the sensorimotor network in patients with CD. […] The mechanism of DBS in CD treatment is unknown. In a single case report, pain improvement with DBS of the globus pallidus internus (GPi) could be temporally dissociated from motor and postural improvement, suggesting that dysfunction of motor and somatosensory circuits in CD is not always in parallel. […] Further research is needed to compare efficacy of available botulinum neurotoxins on pain reduction and long-term benefits.

• #78 Cervical dystonia pathophysiology and treatment options – PubMed

  https://pubmed.ncbi.nlm.nih.gov/11708764/

  Unless the aetiological investigation reveals a specific therapeutic intervention, therapy for CD is symptomatic. It includes supportive therapy and counselling, physical therapy, pharmacotherapy, chemodenervation [botulinum toxin (BTX), phenol, alcohol], and central and peripheral surgical therapy. The most widely used and accepted therapy for CD is local intramuscular injections of BTX-type A. Currently, both BTX type A and type B are commercially available, and type F has undergone testing. Pharmacotherapy, including anticholinergics, dopaminergic depleting and blocking agents, and other muscle relaxants can be used alone or in combination with other therapeutic interventions. Surgery is usually reserved for patients with CD in whom other forms of treatment have failed.

• #79 Recovery From Cervical Dystonia With Topiramate | Putkonen | Journal of Medical Cases

  https://www.journalmc.org/index.php/jmc/article/view/2088/1606

  Primary cervical dystonia (CD), spasmodic torticollis, is the most common focal dystonia. […] CD is associated with reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] The pathophysiology of involuntary movements in dystonia and chorea, essential tremor, myoclonus and restless legs syndrome has been associated with a reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] Topiramate, a sulfamate-substituted monosaccharide, modulates both GABAergic and glutamatergic neurotransmission, as well as voltage-gated ion channels or intracellular signaling pathways. […] This case demonstrates that some patients recover from CD during treatment with topiramate, and remain asymptomatic for years. […] This is in accordance with the pharmacodynamic mechanisms of topiramate, the pathophysiological mechanisms of involuntary movements, and with the clinical evidence of topiramate in some other hyperkinetic movement disorders with similar pathophysiology. […] It would be important to conduct randomized controlled studies of topiramate in CD, and to define the subgroups who may benefit from it.

• #80 Recovery From Cervical Dystonia With Topiramate | Putkonen | Journal of Medical Cases

  https://www.journalmc.org/index.php/jmc/article/view/2088/1606

  Primary cervical dystonia (CD), spasmodic torticollis, is the most common focal dystonia. […] CD is associated with reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] The pathophysiology of involuntary movements in dystonia and chorea, essential tremor, myoclonus and restless legs syndrome has been associated with a reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] Topiramate, a sulfamate-substituted monosaccharide, modulates both GABAergic and glutamatergic neurotransmission, as well as voltage-gated ion channels or intracellular signaling pathways. […] This case demonstrates that some patients recover from CD during treatment with topiramate, and remain asymptomatic for years. […] This is in accordance with the pharmacodynamic mechanisms of topiramate, the pathophysiological mechanisms of involuntary movements, and with the clinical evidence of topiramate in some other hyperkinetic movement disorders with similar pathophysiology. […] It would be important to conduct randomized controlled studies of topiramate in CD, and to define the subgroups who may benefit from it.

• #81 Torticollis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1152543-overview

  As a neurodegenerative disease, torticollis, or idiopathic cervical dystonia, is believed to arise from basal ganglia circuit abnormalities stemming from selective vulnerability of these structures to an abnormal biochemical process that leads to neuronal dysfunction. […] The use of selective D2 ligands with single-photon emission computerized tomography (SPECT) scanning in 10 patients with torticollis has shown reduced D2-receptor binding in the basal ganglia. […] The implication is that underactivity occurs in the D2 dopamine receptors located in the indirect pallidal outflow pathway in both conditions. Such underactivity can be expected to cause disinhibited thalamocortical output and dystonic postures. […] This relative imbalance between direct (D1-related) and indirect (D2-related) pallidal outflow pathways explains the failure of levodopa to adequately improve torticollis and the transient improvement from traditional neuroleptic agents, which initially may reduce D1 activity and eventually both D1 and D2 activity in both pathways. […] Pramipexole is a dopamine agonist with selective, highly potent binding properties to D2 and D3 receptors. […] Further studies of receptor binding are needed to clarify the unknown process leading to the slow evolution and progression of torticollis.

• #82 Torticollis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1152543-overview

  As a neurodegenerative disease, torticollis, or idiopathic cervical dystonia, is believed to arise from basal ganglia circuit abnormalities stemming from selective vulnerability of these structures to an abnormal biochemical process that leads to neuronal dysfunction. […] The use of selective D2 ligands with single-photon emission computerized tomography (SPECT) scanning in 10 patients with torticollis has shown reduced D2-receptor binding in the basal ganglia. […] The implication is that underactivity occurs in the D2 dopamine receptors located in the indirect pallidal outflow pathway in both conditions. Such underactivity can be expected to cause disinhibited thalamocortical output and dystonic postures. […] This relative imbalance between direct (D1-related) and indirect (D2-related) pallidal outflow pathways explains the failure of levodopa to adequately improve torticollis and the transient improvement from traditional neuroleptic agents, which initially may reduce D1 activity and eventually both D1 and D2 activity in both pathways. […] Pramipexole is a dopamine agonist with selective, highly potent binding properties to D2 and D3 receptors. […] Further studies of receptor binding are needed to clarify the unknown process leading to the slow evolution and progression of torticollis.

• #83 Cervical Dystonia: Symptoms, Causes, Treatment

  https://www.verywellhealth.com/cervical-dystonia-7371429

  Cervical dystonia is a neurological condition affecting approximately 60,000 people in the United States. […] The exact cause of cervical dystonia is unknown. However, certain risk factors can increase your chances of developing this condition. Cervical dystonia is more common among 40- to 60-year-old people assigned female at birth and people with a family history of the condition. […] Cervical dystonia can also be a secondary condition caused by other medical problems, such as stroke, Parkinson’s disease, traumatic brain injury, previous neck injury, and conditions that affect the basal ganglia (located at the base of the brain). […] Deep brain stimulation (DBS) is a surgical procedure that can treat cervical dystonia. It involves placing electrodes into brain structures on both sides of the brain.

• #84 Evaluation of outcome of different neurosurgical modalities in management of cervical dystonia | The Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Full Text

  https://ejnpn.springeropen.com/articles/10.1186/s41983-022-00493-7

  Bilateral GPi DBS can be recommended as the first line of management for patients with cervical dystonia as cervical dystonia patients have bilateral basal ganglia dysfunction, thus justifying their improvement when undergoing bilateral surgical intervention as in GPi DBS, as bilateral pallidotomy is not recommended owing to the associated high morbidity and complications. […] The aim of this study was not to compare the postoperative outcome between DBS, pallidotomy, and selective peripheral denervation, however, different surgical options included in our study were associated with significant improvement in patients symptoms with minimal adverse effect.

• #85

  https://practicalneurology.com/articles/2020-oct/movement-disorders-moment-treatment-approaches-to-cervical-dystonia

  Mechanism of Action. Botulinum toxin acts on CD by reducing excessive tone through acetylcholine inhibition to alleviate painful muscle spasms. Muscle atrophy is observed after 2 weeks with subsequent recovery of approximately 80% of muscle mass over the next 12 to 14 weeks is thought to contribute to decompression of nerves, increased tissue perfusion, and improved muscle metabolism. Pain relief, however, is not associated with dose, suggesting pain improvement is not related only to muscle weakening. A central mechanism of pain relief is also hypothesized considering that botulinum toxin is associated with partial normalization of brain activity and connectivity within the basal ganglia and the sensorimotor network in patients with CD. […] The mechanism of DBS in CD treatment is unknown. In a single case report, pain improvement with DBS of the globus pallidus internus (GPi) could be temporally dissociated from motor and postural improvement, suggesting that dysfunction of motor and somatosensory circuits in CD is not always in parallel. […] Further research is needed to compare efficacy of available botulinum neurotoxins on pain reduction and long-term benefits.

• #86

  https://practicalneurology.com/articles/2020-oct/movement-disorders-moment-treatment-approaches-to-cervical-dystonia

  Mechanism of Action. Botulinum toxin acts on CD by reducing excessive tone through acetylcholine inhibition to alleviate painful muscle spasms. Muscle atrophy is observed after 2 weeks with subsequent recovery of approximately 80% of muscle mass over the next 12 to 14 weeks is thought to contribute to decompression of nerves, increased tissue perfusion, and improved muscle metabolism. Pain relief, however, is not associated with dose, suggesting pain improvement is not related only to muscle weakening. A central mechanism of pain relief is also hypothesized considering that botulinum toxin is associated with partial normalization of brain activity and connectivity within the basal ganglia and the sensorimotor network in patients with CD. […] The mechanism of DBS in CD treatment is unknown. In a single case report, pain improvement with DBS of the globus pallidus internus (GPi) could be temporally dissociated from motor and postural improvement, suggesting that dysfunction of motor and somatosensory circuits in CD is not always in parallel. […] Further research is needed to compare efficacy of available botulinum neurotoxins on pain reduction and long-term benefits.

• #87

  https://link.springer.com/article/10.1007/s00221-020-05833-8

  The study provided evidence of reversal of abnormally excessive motor cortex plasticity as a possible mechanism of action of GPi DBS for dystonia. […] The progressive time-course of improvement in dystonia symptoms after GPi DBS is well described and the finding of longitudinal changes in experimentally induced motor cortex plasticity suggests a potential mechanistic role. […] GPi DBS reduces ipsilateral excessive cortical activation in premotor and primary motor areas likely through enhanced thalamocortical inhibition. […] GPi DBS exerts potent inhibition of motor symptoms of dystonia and long-term changes in brainstem and spinal excitability, but seems ineffective in altering sensory endophenotypic defects, which supports their probable upstream role in dystonia pathogenesis. […] Dystonia pathophysiology as elucidated by neurophysiology shows wide ranging abnormalities some of which normalise after clinically effective GPi DBS. Excessive motor cortex plasticity and low frequency pallidal output may play a more direct role in generating dystonic movements. GPi DBS reduces the dystonic symptoms, in proportion to reductions in excessive motor cortex plasticity and low-frequency activity suggesting an important mechanistic role.

• #88

  https://link.springer.com/article/10.1007/s00221-020-05833-8

  The study provided evidence of reversal of abnormally excessive motor cortex plasticity as a possible mechanism of action of GPi DBS for dystonia. […] The progressive time-course of improvement in dystonia symptoms after GPi DBS is well described and the finding of longitudinal changes in experimentally induced motor cortex plasticity suggests a potential mechanistic role. […] GPi DBS reduces ipsilateral excessive cortical activation in premotor and primary motor areas likely through enhanced thalamocortical inhibition. […] GPi DBS exerts potent inhibition of motor symptoms of dystonia and long-term changes in brainstem and spinal excitability, but seems ineffective in altering sensory endophenotypic defects, which supports their probable upstream role in dystonia pathogenesis. […] Dystonia pathophysiology as elucidated by neurophysiology shows wide ranging abnormalities some of which normalise after clinically effective GPi DBS. Excessive motor cortex plasticity and low frequency pallidal output may play a more direct role in generating dystonic movements. GPi DBS reduces the dystonic symptoms, in proportion to reductions in excessive motor cortex plasticity and low-frequency activity suggesting an important mechanistic role.

• #89 Dystonia

  https://www.movementdisorders.org/MDS/About/Movement-Disorder-Overviews/Dystonia.htm

  Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. […] The neural mechanism underlying dystonia involves many regions of the central nervous system (particularly: the basal ganglia, cerebellum, supplementary motor areas and sensorimotor cortex) leading to impaired inhibition, abnormal plasticity and sensorimotor dysfunction. […] There are many causes of dystonia. The etiological classification considers two main lines: evidence of nervous system pathology and whether dystonia is inherited or acquired. […] In many cases of isolated dystonia there is no evidence of degeneration or structural lesion (e.g., DYT1, DYT6; formerly called „primary” dystonias). […] Otherwise, there may be evidence of a static structural lesion causing dystonia, as in the case of dystonic cerebral palsy following perinatal brain injury, or of progressive degeneration (e.g., PKAN, PLAN; formerly called „dystonia plus”).

• #90 Adult-Onset Idiopathic Cervical Dystonia – European Medical Journal

  https://www.emjreviews.com/neurology/article/adult-onset-idiopathic-cervical-dystonia-j190422/

  Adult-onset idiopathic focal dystonia is the most common type of primary dystonia, and adult-onset idiopathic cervical dystonia (AOICD) is its most prevalent phenotype. […] Increasing evidence indicates that AOICD is a neurophysiological network disorder of GABAergic inhibition, causing a syndrome of dystonia, mood disturbance, and social cognitive dysfunction, with the superior colliculus playing a central role. […] Although classically considered a basal ganglia disorder, it is likely that superior colliculus dysfunction underlies the motor and non-motor symptoms. […] MRI evidence suggest that AOIFD is a network disorder affecting multiple distinct regions in the brain. […] Functionally, the superior colliculus (SC) likely plays a central role in disease mechanism, and this has been corroborated, particularly through utilisation of temporal discrimination.

• #91 Advances in Our Understanding of Dystonia— Pathophysiology and Treatment Options – touchNEUROLOGY

  https://touchneurology.com/movement-disorders/journal-articles/advances-in-our-understanding-of-dystonia-pathophysiology-and-treatment-options/

  The primary neurophysiologic mechanisms considered to be important in dystonia pathogenesis include decreased cortical inhibition, increased cortical excitability, abnormal sensory processing, and maladaptive cortical plasticity. […] A central role for cholinergic dysfunction in dystonia pathogenesis is suggested by the observation that anticholinergic medications are the most effective pharmacologic agents in improving dystonia symptoms in primary dystonia patients. […] Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter and is also important in shaping plastic responses of the CNS to somatosensory and other stimuli, including the maintenance and plasticity of cortical receptive fields. […] The effectiveness of these classes of drugs is consistent with the findings discussed above of alterations in dopaminergic and cholinergic neurotransmission and reduced GABA-mediated inhibition in the dystonic CNS.

• #92 Spasmodic torticollis – Wikipedia

  https://en.wikipedia.org/wiki/Spasmodic_torticollis

  The pathophysiology of spasmodic torticollis is still relatively unknown. Spasmodic torticollis is considered neurochemical in nature, and does not result in structural neurodegenerative changes. […] Studies have suggested that there is a functional imbalance in the striatal control of the globus pallidus, specifically the substantia nigra pars reticulata. The studies hypothesize the hyper activation of the cortical areas is due to reduced pallidal inhibition of the thalamus, leading to over activity of the medial and prefrontal cortical areas and under activity of the primary motor cortex during movement. […] It has also been suggested that the functional imbalance is due to an imbalance of neurotransmitters such as dopamine, acetylcholine, and gamma-aminobutyric acid. These neurotransmitters are secreted from the basal ganglia, traveling to muscle groups in the neck. An increase in neurotransmitters causes spasms to occur in the neck, resulting in spasmodic torticollis.

• #93 Recovery From Cervical Dystonia With Topiramate | Putkonen | Journal of Medical Cases

  https://www.journalmc.org/index.php/jmc/article/view/2088/1606

  Primary cervical dystonia (CD), spasmodic torticollis, is the most common focal dystonia. […] CD is associated with reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] The pathophysiology of involuntary movements in dystonia and chorea, essential tremor, myoclonus and restless legs syndrome has been associated with a reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] Topiramate, a sulfamate-substituted monosaccharide, modulates both GABAergic and glutamatergic neurotransmission, as well as voltage-gated ion channels or intracellular signaling pathways. […] This case demonstrates that some patients recover from CD during treatment with topiramate, and remain asymptomatic for years. […] This is in accordance with the pharmacodynamic mechanisms of topiramate, the pathophysiological mechanisms of involuntary movements, and with the clinical evidence of topiramate in some other hyperkinetic movement disorders with similar pathophysiology. […] It would be important to conduct randomized controlled studies of topiramate in CD, and to define the subgroups who may benefit from it.

• #94

  https://journals.lww.com/co-neurology/fulltext/2014/08000/Dystonia___an_update_on_phenomenology,.14.aspx?generateEpub=Article%7Cco-neurology:2014:08000:00014%7C10.1097/wco.0000000000000114%7C

  Based on phenomenology, a new consensus update on the definition, phenomenology and classification of dystonia and a syndromic approach to guide diagnosis have been proposed. […] The recently discovered genes ANO3, GNAL and CIZ1 appear not to be a common cause of adult-onset cervical dystonia. […] The identification of new genes will facilitate better elucidation of pathogenetic mechanisms and possible corrective therapies.

• #95 Frontiers Publishing Partnerships | Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia

  https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2022.10283/full

  Accurate phenomenological characterization of AMs may improve our understanding of their underlying mechanisms. […] Future research should clarify the relative contributions of sensory processing and motor preparation to the different types of AMs, particularly noting the varying complexity of motor organization across AMs. […] In conclusion, our observational study supports the existence of different AMs that are phenomenologically different and could be related to different degrees of dysfunction of sensorimotor integration.

• #96 The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia | Journal of Neuroscience

  https://www.jneurosci.org/content/33/47/18358

  This organization allows for afferent input from a wide range of head and neck structures to influence excitability of TSNC neurons, and for TSNC neurons to modulate activity in cranial and cervical muscles. […] The model proposes a potential role of the TSNC in an integrated functional neural network that may contribute to the underlying pathophysiology of craniocervical dystonia. […] Aberrant trigeminal reflexes are apparent in people who experience blepharospasm, and oromandibular, cranial, and cervical dystonia, with loss of reflex inhibition and increased reflex facilitation. […] We present an integrated network model that includes the TSNC in the pathogenesis of craniocervical dystonia. The proposed model explains how TSNC disinhibition can impact the excitability of motoneurons innervating facial and cervical muscles, both directly and indirectly via neural connections with the motor cortex, basal ganglia, and cerebellum. […] If potentiation of the TSNC contributes to the expression of cranio-cervical dystonia, the trigeminal nerve and sensory nuclear complex may provide a novel therapeutic target.

• #97 Frontiers Publishing Partnerships | Observing the Diversity of Alleviating Manoeuvres in Cervical Dystonia

  https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2022.10283/full

  Accurate phenomenological characterization of AMs may improve our understanding of their underlying mechanisms. […] Future research should clarify the relative contributions of sensory processing and motor preparation to the different types of AMs, particularly noting the varying complexity of motor organization across AMs. […] In conclusion, our observational study supports the existence of different AMs that are phenomenologically different and could be related to different degrees of dysfunction of sensorimotor integration.

• #98

  https://practicalneurology.com/articles/2020-oct/movement-disorders-moment-treatment-approaches-to-cervical-dystonia

  Mechanism of Action. Botulinum toxin acts on CD by reducing excessive tone through acetylcholine inhibition to alleviate painful muscle spasms. Muscle atrophy is observed after 2 weeks with subsequent recovery of approximately 80% of muscle mass over the next 12 to 14 weeks is thought to contribute to decompression of nerves, increased tissue perfusion, and improved muscle metabolism. Pain relief, however, is not associated with dose, suggesting pain improvement is not related only to muscle weakening. A central mechanism of pain relief is also hypothesized considering that botulinum toxin is associated with partial normalization of brain activity and connectivity within the basal ganglia and the sensorimotor network in patients with CD. […] The mechanism of DBS in CD treatment is unknown. In a single case report, pain improvement with DBS of the globus pallidus internus (GPi) could be temporally dissociated from motor and postural improvement, suggesting that dysfunction of motor and somatosensory circuits in CD is not always in parallel. […] Further research is needed to compare efficacy of available botulinum neurotoxins on pain reduction and long-term benefits.

• #99 Recovery From Cervical Dystonia With Topiramate | Putkonen | Journal of Medical Cases

  https://www.journalmc.org/index.php/jmc/article/view/2088/1606

  Primary cervical dystonia (CD), spasmodic torticollis, is the most common focal dystonia. […] CD is associated with reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] The pathophysiology of involuntary movements in dystonia and chorea, essential tremor, myoclonus and restless legs syndrome has been associated with a reduction of gamma-aminobutyric acidergic (GABAergic) neurons in the basal ganglia. […] Topiramate, a sulfamate-substituted monosaccharide, modulates both GABAergic and glutamatergic neurotransmission, as well as voltage-gated ion channels or intracellular signaling pathways. […] This case demonstrates that some patients recover from CD during treatment with topiramate, and remain asymptomatic for years. […] This is in accordance with the pharmacodynamic mechanisms of topiramate, the pathophysiological mechanisms of involuntary movements, and with the clinical evidence of topiramate in some other hyperkinetic movement disorders with similar pathophysiology. […] It would be important to conduct randomized controlled studies of topiramate in CD, and to define the subgroups who may benefit from it.

• #100 Advances in Our Understanding of Dystonia— Pathophysiology and Treatment Options – touchNEUROLOGY

  https://touchneurology.com/movement-disorders/journal-articles/advances-in-our-understanding-of-dystonia-pathophysiology-and-treatment-options/

  Although the pathophysiology of dystonia remains incompletely understood, advances in two major areas of research over the past two decades have led to important insights into the mechanisms of dystonia. […] Ultimately, a more complete understanding of the pathophysiology of dystonia should lead to better, more rational, targeted therapies. […] Although the basal ganglia is clearly a crucial brain region, abnormalities exist in many other regions throughout the motor circuit. […] The existence of dystonia endophenotypes in genetic forms of dystonia, i.e. abnormalities related to the gene mutation regardless of clinical manifestation of dystonia, suggest that it may be a second hit disorder in which genetically predisposed brains can be thrown into an unbalanced dystonic state by environmental or genetic factors.

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