Childhood Dystonia Research Articles

DOPA-sensitive progressive dystonia of childhood with fluctuations of symptoms--Segawa's syndrome and possible variants. Results of a collaborative study of the European Federation of Child Neurology Societies (EFCNS).

Twenty children with dystonia sensitive to L-Dopa were identified in a collaborative study by 11 European colleagues. Most cases showed clinical characteristics similar to those described by Segawa (age and mode of onset, marked diurnal fluctuations, predominant limb involvement with no or minimal axial dystonia and, in all cases, dramatic relief of symptoms with small doses of L-Dopa). The typical diurnal fluctuation of symptoms was not observed in 7 children. Significant differences in this respect were noted among affected siblings. There were 9 sporadic and 11 familial cases. The pedigrees observed do not contradict nor clearly confirm Segawa's hypothesis that this might be a dominantly inherited disorder with low penetrance. Response to low doses of L-Dopa was usually dramatic, the benefit was maintained over periods ranging from one to eight years without complications. Recurrence of symptoms on withdrawal was observed in all cases in which it was attempted. These cases represent a form of progressive, presumably hereditary, childhood dystonia, similar to that originally described in Japan and different from dystonia musculorum deformans. The absence of fluctuations of symptoms despite good L-Dopa response and the great variability in the severity of the disorder were important features which will require further study as will the homogeneity of the syndrome, the mode of genetic transmission and the need for persistent L-Dopa treatment in adult life.

Ventricular fluid somatostatin concentration decreases in childhood-onset dystonia.

Somatostatin was measured in CSF from individuals with a variety of neurologic diseases. In ventricular CSF, somatostatin concentration was significantly lower in individuals with childhood-onset dystonia than in individuals with other forms of dystonia or with other disorders. Severity of childhood dystonia correlated with somatostatin concentration, suggesting a progressive dysfunction of somatostatin-containing neurons with increasing disease severity. There were no significant differences in somatostatin concentration in lumbar CSF. Multiple forms of immunoreactive somatostatin were found in a pool of lumbar CSF from normal individuals. Labeled somatostatin administered intra-arterially to rats failed to cross the blood-brain barrier.

Decreased ventricular fluid norepinephrine metabolite in childhood-onset dystonia.

3-methoxy-4-hydroxyphenylglycol (MHPG), the primary brain metabolite of norepinephrine (NE), was measured in ventricular fluid from 51 patients with dystonia, other movement disorders, or hydrocephalus. The dystonic patients were divided into three categories: childhood-onset form with early limb dystonia and rapid progression to generalized symptoms, more localized and benign adult-onset dystonia, and symptomatic dystonia. Patients with the childhood form had significantly lower ventricular fluid MHPG levels (8.7 +/- 0.6 ng per milliliter) than other dystonic patients (11.4 +/- 1 ng per milliliter), age-matched controls with neurologic disease (11.7 +/- 1.1 ng per milliliter), or other movement disorders (11.8 +/- 0.7 ng per milliliter). Decreased ventricular fluid MHPG levels suggest a possible abnormality of brain NE function in childhood dystonia.

Progressive dystonia and dyskinesia in childhood. A review of some recent advances.

ABSTRACT. The concept of dystonia and dyskinesia is discussed and glutaric aciduria and dystonia musculorum deformans are reviewed as examples of progressive conditions in childhood showing these symptoms. For the latter condition, which is also called idiopathic torsion dystonia, evidence is brought forward that it can be regarded as a disorder of neurotransmittor function of the basal ganglia with “hyperfunction” of the dopamine‐transmitted functions.

A genetic study of torsion dystonia.

A family study of 32 patients with torsion dystonia has shown at least two forms of generalized dystonia with onset in childhood. These two forms, an autosomal dominant and an autosomal recessive, are clinically indistinguishable. There were at least three families and probably about six to eight patients with the autosomal recessive variety. The remaining nine to 11 patients with generalized childhood dystonia are thought, because of a probable paternal age effect, to be examples of new dominant mutations. Since fitness with childhood onset is 1/20 of normal, most childhood dominant cases appear sporadically. Most of the other 15 patients (12 with onset in adult life) appear to have a non-genetic torsion dystonia, although an example of a benign adult-onset dominant form associated with a tremor has been observed. It is concluded that there are at least two forms of genetic torsion dystonia, an autosomal recessive form with onset in childhood, which, on evidence from America, is particularly common in Ashkenazi Jews, and one or more dominant forms, with onset in childhood or adult life. The majority of adult-onset isolated cases of idiopathic torsion dystonia seem to be due to exogenous but unidentified causes.