Focal dystonia (FD) refers to involuntary muscle contractions affecting well-defined muscle groups or even single muscles. Common variants of the disease include cervical dystonia or spasmodic torticollis, benign essential blepharospasm, oromandibular dystonia or Meige syndrome, spasmodic dysphonia, and a series of occupational FD related to specific movements. The pathogenesis of FD has not yet been understood, and treatment is merely symptomatic. Botulinum toxin injections are the mainstay of therapy.
FD patients claim uncontrollable muscle contractions affecting specific parts of their body. These contractions may be sustained or intermittent, i.e., patients may present with dystonic postures, repetitive movements, or any combination thereof. On the other hand, FD may manifest in the failure of willed activity to occur. Dystonic muscle activity may be accompanied by pain and is often triggered by voluntary actions and associated with overflow muscle activation . Conversely, patients may apply certain sensory tricks to alleviate symptoms and break spasms. Touching, smiling, talking, and singing may serve to ameliorate FD. Every area of the body may be affected by FD, but there are common types of the disease which are referred to with specific terms.
While those suffering from cervical dystonia may describe their head to be forced into rotative movements and an abnormal posture, involuntary eyelid closure and an increased spontaneous blink rate are the clinical hallmarks of benign essential blepharospasm. Both eyelids are affected, and severe cases of blepharospasm may render the affected individuals functionally blind. Rapid, forced blinking and intermittent blepharospasm are similarly characteristic of oromandibular dystonia. The latter tends to spread from the eyes to the lower facial musculature, resulting in masticatory, lingual, pharyngeal or laryngeal muscle contractions and movements. Isolated spasms of the laryngeal muscles may result in spasmodic dysphonia, which is characterized by irregular and uncontrolled voice breaks and possibly vocal tremor .
Furthermore, there are reports on distinct types of focal hand dystonias. These are usually related to the performance of specific, complex, and exacting tasks, such as writing (resulting in writer's cramp) and playing an instrument (musician's dystonia). Less frequent focal hand dystonias are observed in typists and telegraphers, who may report abnormal postures of the hand owing to painful muscle spasms, or golfers suffering from golfer's yips. While the etiology of focal hand dystonias remains incompletely understood, the prolonged and intensive practice of the respective tasks seems to be a major risk factor .
FD may be accompanied by limb tremor and psychiatric symptoms such as anxiety and depression . It remains unclear whether psychiatric disturbances contribute to the onset of FD, are provoked by a common cause, or present a consequence associated with stress and stigma .
The diagnosis of FD is based on clinical findings; the differentiation between primary and secondary disorders requires the latter to be confirmed or ruled out. Laboratory analyses of blood and cerebrospinal fluid samples, diagnostic imaging, and further measures may be carried out to this end. They may reveal metabolic disorders, infections, autoimmune diseases, neoplasms, infarctions, hemorrhages, traumatic or degenerative changes, and a variety of other conditions that may explain the neurological deficits . Since dystonia-like symptoms may be induced by distinct compounds, the practical workup of FD cases should always be preceded by a thorough anamnesis. The patient should be queried about the consumption of pharmaceuticals or drugs and any exposure to chemicals. During anamnesis, they should also be asked for a possible family history.
Up to 25% of FD patients have a family history of dystonia . This implies a genetic component in the pathogenesis of the disease, so genetic studies may be useful to identify patients at risk and to confirm a tentative diagnosis. To date, molecular screenings are not part of the general workup of the more common adult cases, but they are definitely recommended in pediatric patients with a positive family history of dystonia .
- White Matter Lesions
Our patients did not have a focal lesion; one had scattered white matter lesion and the other had a diffuse frontoparietal atrophy. [ncbi.nlm.nih.gov]
MRI brain showed a small area of gliosis in the left frontal subcortical white matter but with no lesions in the basal ganglia or thalamus. The dystonia in our patient almost completely resolved with botulinum toxin therapy. [ncbi.nlm.nih.gov]
FD tend to follow a chronic, often progressive course. Most patients require treatment throughout life, but causal therapies are not available. Botulinum toxin injections are the standard approach to therapy. The toxin interferes with the release of acetylcholine at the neuromuscular junction and thus impedes signal transduction from the overactive motor neurons, resulting in persistent muscle relaxation. In terms of dosage and treatment frequency, the response of the individual patient should be considered. Most patients require four injections per year. Botulinum toxin injections are effective and safe, but they are no universal remedy: Patients may not respond to treatment or develop resistance in the long term. Additionally, a minority of patients experiences side effects due to the functional failure of the respective muscles .
More recent approaches to FD consist in transcranial magnetic stimulation, transcranial direct-current stimulation, and deep brain stimulation, and they are mainly employed in patients with disabling dystonias  . Surgery may be considered in refractory cases. Surgical interventions may consist in myectomy or neurectomy, and they may be complemented by functional restorations. Prior to the decision for surgery, every possible effort should be made to alleviate the patient's complaints through symptomatic topical and systemic treatment. In this context, symptomatic therapy may include any measure to avoid environmental conditions known to trigger the onset of muscle contractions. Finally, the psychiatric disturbances observed in FD patients may warrant the administration of antidepressants and anxiolytics.
The segmental spread of FD is a dreaded complication of the disease. It is most commonly observed in patients suffering from oromandibular dystonia, benign essential blepharospasm, and spasmodic dysphonia . Age is considered an important risk factor for segmental spread: The earlier symptoms manifest, the more likely they are to spread. Notwithstanding, isolated FD is a socially debilitating disorder and may induce physical disabilities regardless of spread . There is currently no chance for cure, but the aforementioned treatment regimens are usually effective and give back quality of life. Psychological support is essential to improve the perceived treatment response and should be offered to all patients. Indeed, psychiatric comorbidities have been proven to be the most important determinants of quality of life in patients with dystonia .
Whereas secondary FD is related to neurological injuries or disease processes, primary FD is deemed idiopathic. Hereditary conditions are assumed to be the main cause of primary FD, which have recently been classified as autosomal dominant disorders with markedly reduced penetrance . Although a number of genes have been implicated in the pathogenesis of primary FD, genotype-phenotype correlations and modulating factors remain largely unclear  . Infectious diseases, pregnancy and parturition as well as other stressful situations have been discussed in this context . The overuse of certain muscles may similarly predispose to the disease, as is most evident in focal hand dystonias affecting certain professions.
Due to the heterogeneous presentation of FD, reliable data on the disease' epidemiology cannot be presented. In Ireland, the prevalence of FD has been estimated to 18 per 100,000 inhabitants, and values in the same order of magnitude have been reported decades ago for the United States  . However, back then as well as today, mild cases frequently remain undiagnosed . Furthermore, there are considerable geographic variations: Benign essential blepharospasm, for instance, is more prevalent in lower latitudes with high solar insolation . Contrary to generalized dystonia, FD usually manifests in mid to advanced adulthood, and most types of FD preferentially affect women  .
Disturbances in sensorimotor integration are the pathophysiological basis of FD. Sensorimotor integration requires the comparison of sensory information expected from certain movements with sensory information obtained during the execution of these movements. If any unexpected sensory information is perceived during these movements, they can be modified in order to achieve their original target .
There is no one disturbance of sensorimotor integration that would account for FD. On the contrary, cervical dystonia, benign essential blepharospasm, and other variants of the disease have been linked to different dysfunctions of sensorimotor integration and the corresponding neural circuits for movement . These circuits may be fed with abnormal sensory input, may induce abnormally high activity in the thalamus and cortex, or may be defective due to neuroanatomical anomalies .
In general, FD is believed to be caused by the hyperexcitability of brainstem neurons, which, in turn, results from basal ganglia dysfunctions . Abnormalities in dopamine and GABA signaling have been speculated to account for these dysfunctions . These neurotransmitters are involved in the direct and indirect pathways, which pass through parts of the basal ganglia, sending inhibitory signals from the globus pallidus to the thalamus and cortex  . In detail, overactivity of the indirect and direct pathways entails reduced activity in the internal globus pallidus and thus enhances thalamocortical activation.
The involvement of additional brain regions, like the cerebellum, has been shown for certain types of FD and may even be a universal feature .
Due to considerable knowledge gaps regarding the etiology and pathogenesis of FD, no recommendations can be given to prevent the onset of symptoms. FD patients may, however, observe their environment and try to recognize those stimuli that trigger the acute onset of muscle spasms. Such stimuli may be of tactile, visual, auditory or other nature, or may consist in movements. The avoidance of the respective stimuli may require adaptations in lifestyle, but they may significantly improve the patient's quality of life: Those suffering from benign essential blepharospasm are generally recommended to avoid bright light, and focal hand dystonias may improve upon the reduction of exercise intensity.
In general, dystonia refers to sustained muscle contractions resulting in twisting movements or abnormal postures. Dystonia may affect single muscle groups, entire segments of the body, one of its sides, or several segments located on both of its sides. Accordingly, FD is distinguished from segmental dystonia, hemidystonia, and generalized dystonia . It is currently assumed that these variants of dystonia are part of a continuous spectrum of severity, and this hypothesis is supported by the fact that FD may turn into segmental dystonia. This is referred to as segmental spread and is more commonly observed in patients diagnosed at young ages . In general, FD is a late-onset type of dystonia. If observed in pediatric patients, it may merely be the initial manifestation of a more severe disease .
In sum, the molecular mechanisms behind dystonias are poorly understood. Further research is required for a better comprehension of its causes and progression over time, with such knowledge being indispensable for the development of therapies. To date, only symptomatic treatment can be provided, and patients may experience severe limitations in their everyday and working life.
Focal dystonia (FD) refers to sustained or intermittent, involuntary muscle contractions occurring in a specific part of the body. The most common type of FD is cervical dystonia, which has previously been referred to as spasmodic torticollis. Patients with cervical dystonia suffer from spasms of the cervical musculature forcing them to turn their head into an abnormal posture. Another variant of the disease affects those muscles mediating eyelid closure. These patients are diagnosed with benign essential blepharospasm, and in severe cases, the disease may render them functionally blind. FD may also affect the lower facial musculature, as in oromandibular dystonia or Meige syndrome, or provoke spasmodic dysphonia with irregular voice breaks. Furthermore, the repetitive execution of specific, complex tasks, such as writing or playing an instrument, may result in focal hand dystonias like writer's cramp or musician's dystonia.
The causes of FD remain incompletely understood. A variety of genetic, environmental, and psychological factors may be implicated in the disease process, and it's likely they interact multiplicatively. The lack of knowledge regarding the origin of the disease has hampered all efforts to develop causal therapies, so only symptomatic treatment can be provided. Botulinum toxin injections are the mainstay of FD therapy; they are usually administered in intervals of several months and bring about persistent muscle relaxation.
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