Dystonia Musculorum Research Articles

Multiple Sclerosis and Rheumatoid Arthritis

Eight cases of persistent dystonia appearing one to 14 years after non-progressive cerebral insults are described. Five were due to perinatal anoxia, one to trauma, and two to cerebral infarction. This phenomemon of delayed-onset dystonia has not been described previously, although review of earlier literature reveals several probable examples. Delayed-onset dystonia due to perinatal anoxia is an important diagnostic alternative to dystonia musculorum deformans for dystonia occurring in childhood.

Amino acid changes in the mouse mutant dystonia musculorum similar to those in Friedreich's ataxia.

An autosomal recessive mutant strain of mouse with a progressive neurological disorder is described. Histopathology is dramatic in the sensory afferents and in the red nucleus. In the cerebellar vermis the concentrations of glutamate, aspartate, glycine and GABA are significantly reduced, and in the cerebellar hemispheres the taurine/glutamate ratio is elevated. These mice may provide a useful experimental model of Friedreich's ataxia.

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.

Dystonia musculorum deformans with hyperuricaemia — study of a family

This article presents a study of a family in which association of hyperuricaemia and more interestingly increased C.S.F. uric acid was noticed in two members who had classical dystonia musculorum deformans (DMD). Other members of the family had no clinical evidence of DMD but had increased serum and C.S.F. uric acid. Investigations did not reveal any of the common disorders of the purine metabolism in any of the family members. An attempt has been made to discuss the aetiopathological correlation.

61 BEHAVIORAL MEDICINE ASSESSMENT IN DySTONIA MUBOULORUM DEFORMANS

The assessment of movement disorders necessitates the quantification of abnormal findings. The development of behavior analysis techniques offers a methodology for examining movements. The present study is an attempt to apply behavior analysis techniques to the treatment of disorders. Three patients with Dystonia Musculorum Deformans (age range 16-24y ) were assessed during treatment with artane (8-15mg/d),parsidol (200-400mg/d) (P), tegretol (.4-1.5mg/d) (T) or P+T. The results in one patient are shown. Assessment measures including range of motion, finger dexterity, writing skills, and surface EMG suggests the greatest improvement is on a combination of P+T. This approach suggests that assessment of behavioral changes may provide important information upon which to base clinical decisions. Empirical analysis of behaviors represents a methodology by which treatment efficacy may be quantified and clinical impressions substantiated.

Phosphoprotein phosphatase activity in normal and dystonic human fibroblast plasma membranes.

There is increasing evidence that the level of membrane protein phosphorylation may be related to the regulation of membrane function. We have characterized the phosphoprotein phosphatase activity in membranes prepared from normal human skin fibroblast cultures and from patients with dystonia musculorum deformans (DMD). Protein phosphatase activity was linear with time and membrane protein with a broad pH optimum between 6.0 and 7.5. Fluoride, molybdate, and compounds containing a pyrophosphate moiety were inhibitory. There was no significant difference in the Km or Vmax when fibroblast membranes from patients with DMD were compared to those from normal controls.

Segmental demyelination in the peripheral nerves of mice affected by a hereditary neuropathy (dystonia musculorum)

A teased fibre and electron-microscopical study was carried out on the sciatic nerves of mice affected with the peripheral neuropathy in dystonia musculorum. Widespread segmental demyelination was present in all the nerves. Focal axon swellings were also seen, but were relatively scarce and similar in appearance to post-traumatic reactive swellings. The variability of dystonic internodal lengths was indicative of segmental demyelination rather than axonal degeneration. The largely motor fibres of the phrenic nerve were seen to undergo a similar degenerative process, but with a later onset and more gradual progression. Segmental demyelination was found to be present before axon swellings and other degenerative changes became visible in developing phrenic nerve. Demyelination is thus an important pathological process in dystonia musculorum, and the present observations are consistent with a primary segmental demyelinating disorder in dystonic peripheral nerve.

Increased rates of myofibrillar protein breakdown in muscle-wasting diseases.

The excretion of endogenous creatinine and 3-methylhistidine by subjects with muscle diseases has been measured in order to assess muscle mass and fractional rates of myofibrillar protein degradation. Increases in the rates of myofibrillar protein breakdown were observed in all subjects with Duchenne, Becker, autosomal recessive Duchenne-like, and limb-girdle muscular dystrophy; dystrophia myotonica; myotonia congenita; peroneal muscular atrophy; myasthenia gravis; and central core disease; in some cases of spinal muscular atrophy; but in no cases of facioscapulohumeral muscular dystrophy of dystonia musculorum deformans. All increases in myofibrillar protein breakdown were associated with reductions in muscle proportion below the normal. Muscle-wasting diseases may respond to therapy directed towards an inhibition of muscle protease activity; the efficacy of such therapy can be monitored by the 3-methylhistidine-to-creatinine excretion ratio.

An allele of the mouse mutant dystonia musculorum exhibits lesions in red nucleus and striatum

A spontaneously occurring allele of the mouse mutant dystonia musculorum exhibits pathology in the brain as well as in the dorsal root ganglia. In every mutant examined coarse neurons of the red nucleus (which give rise to the rubrospinal tract) exhibited pathological features. In addition, generally less severe and somewhat asymmetric abnormalities occurred in the striatum. Thus, the motor abnormalities seen in the animals may be attributable to multiple pathological alterations.

Peripheral neuropathy in mouse hereditary diabetes mellitus. I. Comparison of neurologic, histologic, and morphometric parameters with dystonic mice.

C57BL/KsJ db/db inbred mice have an hereditary autosomal recessive disease resembling in some respects maturity onset human diabetes mellitus. At 8--11 months of age, they displayed intermittent symptoms suggestive of a mild sensory neuropathy. These symptoms consisted of adduction of their hind limbs and flexing hind paws when raised by the tail, and inability to maintain their position on the roto wheel. Peripheral nerves and sensory ganglia of the diabetic mice were compared with those of the unafflicted littermates and studied with respect to Schwann cell counts and myelinated nerve fiber diameter measurements. In addition, teased fibers of peripheral nerves were compared for obvious changes in internodal distance and demyelination. Chromatolytic neurons were moe abundant in lumbosacral spinal ganglia of diabetic mice than in corresponding ganglia of controls or in more anterior spinal ganglia and trigeminal ganglia of diabetics. Histologic studies showed an increase in Schwann cell counts in longitudinal sections of peripheral nerves. A similar but larger increase was observed in peripheral nerves of mice affected with an hereditary sensory neuropathy, dystonia musculorum. A small but general decrease in myelinated fiber diameter was observed in sensory and motor nerves.

Changes in whole tissue biosynthesis of γ-amino butyric acid (GABA) in basal ganglia of the dystonia (dt Alb) mouse

The mouse mutant dystonia musculorum shows many of the symptoms of of human dystonics. In this study whole tissue samples of mutant striatum and substantia nigra showed almost 50% less γ-amino butyric acid (GABA) biosynthetic capacity than controls of the same inbred strain. Hypothalamic values were unchanged. The defect appears to be one of substrate localization, since both crude extract enzyme activity and the fractional conversion of glutamate to GABA were unaffected by the mutation. When tissue is disrupted, high-affinity synaptosomal uptake to glutamate does not appear to be affected; therefore an endogenous inhibitor of glutamate transport is postulated for the mutant.

MMPI characteristics associated with cerebral palsy and dystonia musculorum deformans.

The origins of dystonia musculorum deformans are now considered to be organic. However, misdiagnosis of dystonia as a functional psychiatric disorder--usually conversion reaction--has persisted. The present study describes personality traits as measured by the Minnesota Multiphasic Personality Inventory in 30 persons with dystonia and in a control group of 37 persons with cerebral palsy. The data, examined by diagnosis, level of disability, and sex, showed no differences for diagnostic groups or levels of disability. Males scored in the direction of greater psychopathology than did females. The male dystonics showed the highest elevations of MMPI scales of all the groups. Although only one person with dystonia musculorum deformans and none with cerebral palsy produced the profile usually associated with conversion reaction, 36% of all profiles showed two scales above a T score of 70. This finding suggested that young adults with a physically disabling disease may be at higher risk for developing maladaptive personality traits.

Treatment of Spasmodic TorticoIIis by DorsaI Column Stimulation

A new method is described to treat spasmodic torticollis with the implantation of a dorsal column stimulator at the C<sub>1–2</sub> level or with transcutaneous stimulation. 22 patients were evaluated. 3 had sufficient relief to be treated with transcutaneous stimulation only. An additional 6 patients had surgically implanted dorsal column stimulators. It was empirically determined that a frequency of 800–1,100 Hz gave the best relief from torticollis. 1 patient had an excellent result; 3 have had good results; 1 had a fair result, and 1 had a poor result. An additional patient with dystonia musculorum deformans was considerably improved by the use of dorsal column stimulation.

Long-term review of dentatectomy in dystonia musculorum deformans and cerebral palsy.

Since 1966 34 patients with disorders of movement and tone due to dystonia musculorum deformans, cerebral palsy and other dyskinesias underwent ablation of the cerebellar dentate nucleus. Long term results (2–8 years) in 19 patients could be verified. Five other patients died and 10 were lost to follow up.

Autosomal dominant striatonigral degeneration

An autosomal dominant striatonigral degeneration is present in a family of Portuguese ancestry numbering in excess of 329 persons in eight generations. The illness begins in the second, third, or fourth decade, and progresses for about 15 years with parkinsonian rigidity, spasticity, spastic dysarthria, and abnormalities of eye movement. Neuropathologic findings are severe neuronal loss and astrocytic gliosis in the corpus striatum and substantia nigra, with a moderate neuronal loss in the dentate nucleus of the cerebellum and nucleus ruber of the midbrain. This is a new genetic entity, distinct from other autosomal dominant neurologic disorders such as nigrospinodentatal degeneration, olivopontocerebellar degeneration, dystonia musculorum deformans, Machado's disease, and Huntington's disease.

HISTOCHEMICAL AND ULTRASTRUCTURAL STUDIES OF PRIMARY SENSORY NEURONS IN MICE WITH DYSTONIA MUSCULORUM. I. ACETYLCHOLINESTERASE AND LYSOSOMAL HYDROLASES

Histochemical and ultrastructural studies of primary sensory neurons in mice with dystonia musculorum. I. Acetylcholinesterase and lysosomal hydrolasesEnzyme histochemical and fine structural studies were performed on mice with a hereditary sensory neuropathy (dystonia musculorum). The dystonic mice were compared with normal litter mates. Acetylcholinesterase activity was studied in trigeminal and spinal ganglia and sensory receptors as well as in sympathetic ganglia. Lysosomal hydrolases and ultrastructural features were studied in the trigeminal and spinal ganglia. Striking changes in the amount and distribution of enzymic activity were observed in the perikarya of sensory ganglion neurons in dystonic mice. Perikaryal involvement was indicated by displacement of the nucleus, enlargement of the perikaryon, peripheral location of Nissl substance, loss of enzymic activity and an increase in the number of neurofilaments–features similar to those that follow physical interruption of the axon. The focal axonal swellings that occurred along sensory nerve fibers contained concentrations of lysosomal hydrolases and sometimes acetylcholinesterase activity. They were generally more numerous in the nerve fibers located distal to the ganglion rather than proximal to it. At the ultrastructural level these swellings contained lysosomal bodies and remnants of organelles. Some abnormalities in the myelin and the size of paranodal gaps were also observed. These results are discussed in relation to interruptions in axoplasmic flow and experimental neuropathies including those of the ‘dying‐back’ type.

Anesthetic management of a patient with dystonia musculorum deformans.

Anesthetic management of a patient with dystonia musculorum deformans.

Lysosomal hydrolases in the trigeminal ganglion of mice afflicted with an hereditary sensory neuropathy (dystonia musculorum).

Selected lysosomal hydrolases have been investigated in the trigeminal ganglion of mice afflicted with an hereditary sensory neuropathy (dystonia musculorum). This was done using direct enzyme histochemistry. Correlative electron microscopy was also used to further elucidate perikaryal changes. The earlies observed lesion in the trigeminal ganglion of afflicted mice was numerous axon swellings containing intense lysosomal hydrolase activity. Subsequent to this observation, numerous neurones showed central chromatolysis, eccentric nucleus and increased lysosomal hydrolase activity. As various neurones throughout the ganglion underwent the classical chromatolytic reaction, the Golgi apparatus moved to a juxtanuclear location, and there was a focal juxtanuclear accumulation of lysosomes. During the later stages of the disease, a striking decrease in neuronal hydrolase activity characteristic of neuronal atrophy was observed. These results are consistent with earlier suggestions that loss of sensation in the disease could be due to an interruption of axonal transport in primary sensory of neurones.

Familial idiopathic basal ganglia calcification exhibiting "dystonia musculorum deformans" features.

Basal ganglia calcifications have been reported in cases of abnormality of parathyroid glands function showing various clinical manifestations. Two cases of familial idiopathic basal ganglia and possibly dentato-rubro-striatum system calcification exhibiting features of ‘dystonia musculorum deformans’ are reported and the pathogenesis of the disease is discussed.

The Victim Is Always the Same

This remarkable little book, absorbing for the physician and sufficiently explicit for the layman, uses an infrequent disease, dystonia musculorum, to show the complementary natures of the science and the art of medicine in the care of all patients. It tells the story of the surgical treatment of involuntary movements, the accidental discovery of the effectiveness of thalamic ablation, and the history, clinical course, and treatment of dystonia musculorum, as well as the ethical aspects of subjecting patients to untried procedures. We are in the homes, hospital, and operating room with three patients and their families: girls of 11 and 14 years, undiagnosed for five and eight years, and a man of 24 undiagnosed for 17 years. We hear how these patients, brushed off by family physicians and specialists who found nothing wrong physically, were subjected to years of inappropriate and traumatic psychotherapy; how a harmonious family was almost destroyed