© Springer-Verlag Italia 2015
Angelo Sghirlanzoni, Giuseppe Lauria and Luisa Chiapparini (eds.)Prognosis of Neurological Diseases10.1007/978-88-470-5755-5_3333. Extrapyramidal Diseases: Dystonia
(1)
Direttore UOC di Neurologia, Ospedale dell’Angelo, Via Paccagnella, 11, Venezia Mestre, 30174, Italy
Keywords
Deep brain stimulationBotulinum toxinKey Facts
Terminology and definitions – Dystonia is a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures.
Clinical features – Dystonia may be: (a) inherited; (b) acquired; (c) idiopathic. Dystonia can also be classified according to etiology, age at onset, body distribution.
–Prevalence of primary (idiopathic) early-onset dystonia is 24–50 cases per million; prevalence of late-onset variants is 101–430 cases per million. Constant or intermittent, involuntary, peculiar movements may be generalized, focal, multifocal, or may be lateralized to one side of the body.
Diagnostic markers
Blood non-specific in primary and idiopathic form.
CSF non-specific in primary and idiopathic form.
Genetics – A specific molecular genetic mutation has been identified for 12 forms; DYT1 is the mutated gene of the early-onset primary dystonia (before age 24 years).
Imaging – TC and MRI non-specific in primary form.
Neurophysiology: not routinely recommended
Therapy –
Medical – Botulinum toxin, anticholinergics, baclofen, benzodiazepines, and others (levodopa, carbamazepine, and dopamine-depleting drugs).
–Surgical – GPi-DBS for primary generalized, cervical dystonia, and other variants. DBS may be useful also in several secondary dystonias.
Prognosis – Primary forms are usually slowly progressive. In most individuals with onset in one leg, dystonia progresses over several years. Prognosis of secondary dystonia depends on the underlying disease.
Abbreviations
BoNT, Botulinum NeuroToxin; CP, Cerebral palsy; DBS, Deep brain stimulation; DRD, Dopa-Responsive Dystonia; GMFCS, Gross Motor Function Classification System; GPi, Globus Pallidus internus; MRI, Magnetic Resonance Imaging; TMS, Transcranial Magnetic Stimulation
33.1 Prognosis of Dystonia
33.1.1 Definition
Dystonia is a movement disorder characterized by uncontrollable sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures [1].
33.1.2 Demographics
The prevalence of early-onset dystonia ranges from 24 to 50 cases per million, with a peak age of onset in the first and second decade of life; the prevalence of late-onset dystonia ranges from 101 to 430 cases per million. Hand dystonia occurs at 30–40 years with male predominance; cranio-cervical dystonia appears in subjects over the age of 40 and is more frequent in women [2].
33.1.3 Clinical Features and Classification
Dystonia can be classified clinically according to age of onset, body distribution, temporal pattern, associated features, and etiology (inherited, acquired, or idiopathic) [1]. Dystonic movements are typically sustained, repetitive, twirling, and may be similar to tremor, which may start or worsen with voluntary activity. Non-motor components of dystonia may be important and include abnormalities in sensory and perceptual functions, as well as in neuropsychiatric, cognitive, and sleep domains [3].
Five features specify clinical characteristics: age at onset, body distribution, temporal pattern of dystonic movements, coexistence of other movement disorders, and additional neurological manifestations [1].
Dystonia that begins in childhood is more likely to have a recognizable cause, and is more likely progressive from focal to generalized. The body distribution of dystonic movements may change over time, typically with progression to previously uninvolved sites [4].
33.2 Genetics
Dystonia is a multifactorial disorder, in which one or more genes combine with environmental factors to reach the threshold of disease.
Regardless of possible underlying genetic abnormality, the pattern of transmission in primary dystonia is autosomal dominant in early- and late-onset dystonia with penetrance rates of 40–60 % and 20 %, respectively [5].
Inherited group
The genetic cause has been identified in 25 forms of dystonia. Autosomal dominant dystonias include the DYT1 form (the most common) and others. The autosomal recessive group includes numerous metabolic disorders.
Acquired group
may be “idiopathic” or due to a known specific cause (perinatal brain injury, infection, psychogenic, etc.)
33.3 Diagnostic Markers
Clinical feature and serial single-gene or multi-gene molecular genetic testing are the main diagnostic tools.
Imaging
Neuroimaging studies are usually normal in idiopathic dystonia and not routinely required. MRI is the investigation of choice in detecting secondary dystonic syndromes.
Neurophysiology
All neurophysiological reports are observational studies without controls (Class IV, level of evidence).
EMG
recordings from various muscles may contribute to the clinical assessment and planning the target of botulinum toxin.
Somatosensory evoked potentials
can detect giant cortical potentials. Sensory perception and somatosensory temporal discrimination threshold abnormalities are a generalized feature of dystonias, and they are a tool for screening subclinical sensory abnormalities [6].
33.4 Therapy
Medical
Anticholinergics, particularly trihexyphenidyl, at a mean dosage of 30 mg/die, are the established first-line oral medications for generalized and segmental dystonia, and can be useful for symptomatic treatment of secondary dystonia. Baclofen, benzodiazepines, and levodopa may be employed.
Tetrabenazine, a presynaptic depleter of dopamine and a weak dopamine-receptor–blocking agent, produced marked improvement in two-thirds of patients with focal and generalized, but was associated with frequent side effects [7]. Levodopa may provide benefit in the dopa-responsive dystonia (DRD), in some patients with DYT1 dystonia and, inconstantly, in secondary forms.
Intrathecal baclofen infusion gave conflicting results in generalized and in secondary dystonias associated to spasticity or pain (cfr. in dystonia from cerebral palsy (CP) [8].
Botulinum Toxin (BoNT) is the first-line treatment for focal and task-specific dystonias.