1/761. Genetic analysis of three patients with an 18p- syndrome and dystonia. Some patients with an 18p- syndrome show dystonia, and a focal dystonia gene has been mapped to chromosome 18p. The authors evaluated the extent of the deletion in three patients with an 18p- syndrome and dystonia using 14 dna markers on 18p. A common deleted area, covering the DYT7 locus, places the putative dystonia gene between the telomere of 18p and D18S1104 (49.6 cM). dystonia in these patients may be caused by haploinsufficiency of the DYT7 gene, a new dystonia gene on 18p, or may result from developmental brain anomalies. ( info) |
2/761. Stereotactic pallidotomy in a child with Hallervorden-Spatz disease. Case report. The authors present a case of Hallervorden-Spatz disease (HSD) in a 10-year-old boy treated with stereotactic pallidotomy for control of severe dystonia. Hallervorden-Spatz disease is a rare type of neuraxonal dystrophy that can be familial or sporadic. This is the first case of HSD reported in the literature in which a pallidotomy was performed. The patient had progressively worsening dystonias and spasms that prevented useful function of his entire right side and eventually threatened his respiratory ability. Pre- and postoperative magnetic resonance images are presented along with electrophysiological recordings made in the globus pallidus at the time of surgery. Functional improvement in the use of the patient's limbs and relief from the painful dystonia were observed. Stereotactic pallidotomy should be considered as a potential treatment in the management of HSD. ( info) |
3/761. Progressive dystonia in a child with chromosome 18p deletion, treated with intrathecal baclofen. We report a case of dystonia with a partial deletion of the short arm (p) of chromosome 18 and androgen insensitivity. Neurologic findings in the 18p syndrome are reported to include mental retardation, seizures, incoordination, tremor, and chorea. A 15-year-old girl with a denovo 18p deletion [karyotype 46, XY, del (18)(p11.1)] developed progressive asymmetric dystonia. She had oromotor apraxia and partial expressive aphasia since childhood, and she was able to partially communicate through elementary sign language. At the age of 15 years, she developed subacute and progressive choreic movements of the right arm, severe dystonic posturing of the left arm, and spastic dystonia in both legs. Her response to parenteral or oral benzodiazepines, oral trihexyphenidyl, benztropine mesylate, baclofen, and L-dopa were brief and inadequate. The response to intrathecal baclofen has been sustained over 18 months. In all likelihood, the 18p deletion syndrome affecting this patient is significant in the pathogenesis of her acquired dystonia. Chronic intrathecal baclofen therapy via pump has been effective in this case and should be considered as a treatment modality in carefully selected patients with dystonia. ( info) |
4/761. Osmotic demyelination syndrome with two-phase movement disorders: case report. Osmotic demyelination syndrome (ODS) is characterized by regions of demyelination throughout the brain, which are most prominent in the pons. This demyelinating disease is associated with electrolyte disturbances and typically occurs in patients who are alcoholic or malnourished. movement disorders are not frequently recognized in patients with ODS. This report describes a 22-year-old woman with ODS after correction of profound hyponatremia. The main neurologic symptom was two-phase movement disorder. First, she had acute onset dystonia, then the movement disorder transformed to generalized rigidity and tremors in the delayed second phase. magnetic resonance imaging in the first phase revealed demyelinating lesions in the central pons, bilateral thalami and basal ganglia. In the second phase, the previous myelinolysis had been partially resolved. The clinical course of the two-phase movement disorder did not correlate with the resolving feature of neuroradiologic findings. During the second-phase movement disorder, the patient had a good response to propranolol and trihexyphenidyl. ( info) |
| A 74-year-old patient suffers from painful muscle cramps when he stands since 30 years. He has no visible tremor but 16 Hz burst activity on EMG, indicating orthostatic tremor. Previous diagnosis was hysteria, stiff person syndrome or dystonia. This shows that EMG during standing should be part of the examination of patients with stiff muscles or muscle cramps. tremor was not strictly orthostatic. It appeared in back muscles while sitting, when the patient supported a weight with outstretched arms. Phase between muscles differed between normal standing and standing on heels. Subthreshold transcranial magnetic stimulation modulated timing of the tremor bursts and inhibited them at higher intensity stimulation. ( info) |
6/761. A novel missense mutant inactivates gtp cyclohydrolase I in dopa-responsive dystonia. Dopa-responsive dystonia (DRD) due to mutant gtp cyclohydrolase I (GCH) shows the considerable heterogeneity of clinical phenotypic expression. To explain the clinical diversity, we studied a Japanese family with a novel mutant GCH (GCH-G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Coexpression experiments using the mutant with wild-type GCH showed that GCH-G90V inactivated the normal enzyme in a dose-dependent manner, suggesting that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms for the clinical heterogeneity of DRD. ( info) |
7/761. GCH1 mutation in a patient with adult-onset oromandibular dystonia. The authors report a mutation in exon 5 of GCH1 in a patient with adult-onset oromandibular dystonia and no obvious family history of dystonia. The patient responded positively to treatment with L-dopa. These findings demonstrate that GCH1 mutations must be considered even in patients with dystonic symptoms not typical of dopa-responsive dystonia. ( info) |
8/761. Follow-up findings in regional cerebral blood flow (r-CBF)-SPECT in a case of idiopathic childhood hemidystonia. functional neuroimaging and pathophysiological implications. A 9 1/2-year-old girl suffered from intermitting tremor and jitteriness of her left hand and oral muscles every 4 to 6 weeks with long lasting episodes. Clinically myoclonias and dystonic positioning of the left arm, hand and facial muscles were seen. No evidence of trauma, infection or inborn errors of metabolism was found. Successful therapy with carbamazepine was initiated while L-DOPA failed. An ictal 99m-Tc-HMPAO-SPECT showed severe asymmetry with focal hyperperfusion of the contralateral right thalamus and basal ganglia as well as of the bifrontal cortex, whereas no anatomical lesions were found by MRI. In contrast, an interictally performed 99m-Tc-HMPAO SPECT showed hypoperfusion of the right thalamus and normalisation of the frontal perfusion under medical treatment. These 99m-Tc-HMPAO-SPECT findings may provide new insights into the localisation and pathophysiological pathways of idiopathic childhood dystonia. ( info) |
9/761. trihexyphenidyl in posthemorrhagic dystonia: motor and language effects. trihexyphenidyl has been found to be an effective treatment for dystonic movement disorders, improving gross motor function in patients with axial and torsional dystonia, tremors, and myoclonus. In this report, improvements in fine motor control, language, and oral motor skills are described with trihexyphenidyl in an 8-year-old female who developed dystonia after spontaneous bilateral putamenal hemorrhages. No adverse side effects occurred. The mechanism of action of trihexyphenidyl is believed to be in the basal ganglia where it inhibits muscarinic cholinergic receptors and increases the turnover of dopamine. ( info) |
10/761. A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form. We found a new mutation in the gtp cyclohydrolase gene involved in dopa-responsive dystonia. We sequenced the gtp cyclohydrolase gene in a family with four siblings affected by this disorder and identified an A-T mutation in exon 2, leading to a non conservative amino acid substitution at codon 135 of the protein (Ile135Lys), which may change the conformation of the binding site of this enzyme. The clinical evolution was heterogeneous among carriers of the same mutation, underlining the involvement of other determinants modulating the occurrence of the disease such as genetic or environmental susceptibility factors. ( info) |