Dystonia

The term dystonia is only very vaguely defined clinically. In fact, it describes several forms of diseases and complaints with different causes and also different clinical symptoms. Dystonia can be an independent disease, such as idiopathic torsional dystonia. This dystonia manifests itself in rotational movements primarily of the torso, neck and extremities, without any identifiable cause. However, dystonia often also describes a clinical syndrome as a result of other underlying diseases, such as symptomatic dystonia after childhood brain damage *.

The classification of dystonia is complex and very confusing even for experts. It is based both on the underlying causes as well as on clinical symptoms and the question which parts of the body are affected and to what extent. Basically, two forms of dystonia can be distinguished *:

1. Primary (idiopathic) dystonia
2. Secondary (symptomatic) dystonia

Primary dystonia occurs independently of an event or other disease. When its cause is unclear, it is called idiopathic dystonia.

Secondary dystonia results from an event or an underlying disease. The dystonia is then only a symptom of that condition. Examples include a lack of oxygen to the brain during birth, encephalitis, traumatic brain injury, or stroke.

Very important for the clinical dystonia classification is also the distribution pattern of involuntary movements. A distinction is made between the following types:

• Generalized dystonia
  Dystonia affects several segments or even non-contiguous areas of the body
• Segmental, multifocal dystonia
  Dystonia affects contiguous body segments (e.g., the entire arm, leg, trunk, neck, etc.).
• Focal dystonia
  A single part of the body is affected by dystonia. Examples of this are writer's cramp (graphospasm), eyelid spasm (blepharospasm), or spasmodic torticollis

Overall, idiopathic focal and segmental dystonias in adults account for the largest proportion of primary dystonia syndromes.

Due to the heterogeneity of what is called dystonia, it is difficult to give exact numbers. According to the Swiss Dystonia Society (SDG), there are an estimated 8000 patients of this rare disease in Switzerland. The disease usually sets in between the ages of 30 and 50. Men and women are affected with equal frequency.

So far, there is no unified model that explains the different forms of dystonia. In recent years, a genetic cause has been found for a growing number of primary dystonias. This was first discovered for idiopathic torsional dystonia, a generalized dystonia (extending to several non-adjacent regions) with onset in childhood. The responsible gene DYT1 is detectable in affected individuals and directly heritable. The role and function of this gene in healthy humans is still the subject of active research.

On the other hand, in secondary dystonia, lesions are often observed in the area of the basal ganglia, a nuclear area in the depth of the cerebrum. The cause of these lesions may be circulatory disturbances, inflammatory diseases, or cerebral hemorrhages. Similar to Parkinson’s disease, dystonia is explained as a disturbance within the complex and finely tuned neuronal network within the basal ganglia, which play a central role in the control and regulation of motor activity.

Furthermore, it has been found that drugs that affect the metabolism of the neurotransmitter dopamine can trigger dystonia. This fits in with the fact that dopamine is an important neurotransmitter within the basal ganglia and has a decisive influence on information processing and can therefore also be causally involved in the development of symptoms.

Dystonia manifests itself in strong, persistent spasms of the skeletal muscles, which the affected person cannot control or influence by will. These contractions are often repetitive, which means that they repeat themselves in rapid sequences. The resulting abnormal postures, twisting movements and sometimes bizarre contortions of individual body parts are often accompanied by pain and severely restrict those affected in their everyday activities. The dystonic symptoms can be intensified by paying attention, emotional arousal and passive movements and subside with sleep and during anesthesia.

If left untreated, dystonia can increasingly lead to the death of muscle tissue, severe contractions, and skeletal deformities such as scoliosis, resulting in disability.

Frequently, patients with dystonia are observed to have an additional tremor. The tremor may be fine-beat (low-frequency) and manifest itself when the hands are actively held, or it may occur as a slower tremor in the dystonic part of the body. The dystonic tremor can sometimes precede the actual dystonia by years and is difficult to diagnose in these cases.

The diagnosis of a dystonic syndrome is made clinically, that is, based on specific questioning of the patient and clinical examination findings. Recognition of typical movement patterns caused by slow repetitive muscle contractions leading to abnormal postures is essential. Other additional neurological symptoms such as paralysis (paresis), abnormal reflexes due to damage of the pyramidal tract (pyramidal tract signs), disturbances of movement coordination (ataxia) or cognitive performance deficits exclude the diagnosis of idiopathic dystonia. Further diagnostic testing should include magnetic resonance imaging (MRI) of the skull to rule out a secondary form of dystonia. In certain cases, genetic testing is also performed.

Causal therapy

Causative treatment is only possible for the rare inherited disorder of L-dopa-sensitive dystonia, also known as Segawa syndrome.

Drug therapy

Since many primary forms of dystonia in childhood respond to dopamine, a drug trial with the drug L-dopa should be at the beginning of treatment in children. In adults, on the other hand, an often protracted L-dopa therapy trial is hardly worthwhile.

Symptomatic therapy

Symptomatic treatment of dystonia is primarily based on the affected body regions. In the case of focal dystonias such as writer's cramp or torticollis, local injections of botulinum toxin are now usually the first-choice therapy to specifically relieve the muscular spasms.

Functional neurosurgical therapy

If drug therapy does not lead to sufficient improvement, surgical procedures can be used. Depending on the form of dystonia, different therapeutic procedures are used.

Stereotactic procedures, especially deep brain stimulation (DBS), are associated with very good treatment success. Stereotactic procedures are minimally invasive procedures in which the patient and the medical instruments are firmly fixed to achieve the highest precision.

At Inselspital, DBS of the globus pallidus internus (GPi) is the surgical procedure of choice. One reason for this is the reversible effect of the stimulation and thus also the possible side effects. By adjusting the stimulation parameters, many side effects such as muscular spasms, light flashes, sensory disturbances, balance and gait disturbances, or speech disorders can be avoided.

The clinical effect of deep brain stimulation for the treatment of dystonia has been demonstrated in clinical randomized controlled trials *. The anti-dystonic effect sets in slowly, over weeks to months.

The improvement of MRI imaging and in particular the development of new sequences such as MDEFT at Inselspital allow a better radiological-anatomical representation of the target structure and thus a more precise implantation *. In special cases, stimulation of the motor thalamus is also a possible alternative, which can be discussed in individual cases *.

Therapy-resistant dystonic tremor also responds to deep brain stimulation. However, the success rate, the clinical effect as well as the long-term results are less good here than in essential tremor  *. The target in this case is the motor thalamus (VIM) or the posterior subthalamic area (PSA). A combination of GPi stimulation and VIM or PSA stimulation must be discussed in individual cases.

Deep brain stimulation (DBS)

In principle, side effects are the same as for all stereotactic functional DBS procedures. Specific risks associated with GPi stimulation for the treatment of dystonia may include transient perceptions of "light flashes" upon stimulation of the optic tract, muscular twitching, speech disorders (dysarthria), or sensory insensations. As a rule, however, these stimulation-induced side effects are reversible.

As with other disorders, the indication for DBS is generally made on an interdisciplinary basis in collaboration with neurologists and neurosurgeons. Extensive examinations, such as neurological examinations, neuropsychological tests, a psychiatric evaluation, and a surgical evaluation are performed in advance. This is to ensure that only patients with very good prospects of improving their symptoms are selected for surgery. At Inselspital, patient cases are discussed individually by our interdisciplinary Movement Disorders Board for this purpose, in order to be able to offer the best therapeutic options to each individual patient.