[Athetosis or dystonia?]. / Athétose ou dystonie?

The term athetosis has progressively disappeared from the anglo-saxon literature which considers that athetosis is part of the spectrum of dystonia. These two clinical entities can be distinguished, however. Athetosis can be identified, searching for subtle semiological traits, in particular at the level of the hand. The earlier appearance of athetosis may be result from its onset during the early phases of development of the central nervous system. Despite its rarity, the clinical diagnosis of athetosis is important to consider from a prognostic point of view. Indeed, it results from brain lesions, and is therefore not a hereditary disorder as it may be the case for dystonia, and its evolution is relatively stable. The efficacy of treatments used in patients with dystonia, in particular high frequency pallidal stimulation, remains to be assessed in patients with athetosis. The concept of athetosis is still helpful in clinical practice.

Clinical characteristics and topography of lesions in movement disorders due to thalamic lesions.

OBJECTIVE: To determine which thalamic subnuclei are involved in symptomatic unilateral movement disorders due to localized thalamic infarction, and the clinical characteristics of these abnormal movements. METHODS: The authors studied 22 patients with thalamic infarcts for their clinical presentation and the topography of the lesions, using three-dimensional T1-weighted MRI sequencing and stereotaxic analysis of the lesions. RESULTS: Patients were divided into four groups: 1) absence of abnormal involuntary movements (AIM) (nine patients); 2) isolated dystonic posture (two patients); 3) myoclonic dystonia (five patients); and 4) tremor or myoclonus (six patients). In patients with AIM, thalamic lesions were contralateral to the abnormal movements, involving the thalamogeniculate territory, centered on the ventral intermediate (Vim) and ventral caudal (Vc) nuclei. No significant difference in the volumes or center of mass of the lesions was found between patients with tremor and myoclonus and patients with dystonia, although the central nucleus and the internal part of the Vim nucleus were more consistently damaged in dystonic patients. CONCLUSION: Movement disorders related to thalamic lesions included: 1) myoclonic dystonia with predominating myoclonus and "thalamic" hand associating dystonic posture and slow, pseudo-athetoid movements, both related to lesions in the Vim and Vc nuclei of the thalamus; and 2) postural and action tremor, also related to lesions in the Vim, similar to tremor associated with midbrain lesions, as a result of abnormal functioning of the cerebello-thalamic pathways.

Selected serum cytokines in systemic lupus erythematosus treated with quinagolide.

The objective of this study was to determine the effect of quinagolide (Norprolac) on serum level of cytokines in systemic lupus erythematosus (SLE) patients. In 20 SLE patients treated with a low dose of quinagolide, and in 17 healthy persons who constituted the control group, concentration of serum prolactin (PRL), interleukins (ILs), soluble tumor necrosis factor receptors (sTNF Rs) preceded by calculation of disease activity index (SLEDAI) were tested at entry and then after 3 months in 16 patients and after 6 months in 11 patients who completed the study. Serum PRL level was higher (though insignificantly) in the SLE group than in the controls and decreased significantly after 6 months of therapy. A raised SLEDAI score at entry was significantly reduced during therapy but a weak correlation with PRL level was revealed. A significant increase in IL-6 level in SLE group as compared to controls was observed (respectively 14.57 +/- 13.25 and 5.04 +/- 3.35 microg/ml) as well as a significantly decreased level after 6 months of treatment (4.30 +/- 2.51 pg/ml). There was a significant difference between sTNF RI concentration before and after 3 months of quinagolide treatment (respectively 1140.83 +/- 312.08 and 1454.58 +/- 465.54 pg/ml). After 6 months of treatment a statistically significant correlation between concentration of PRL and level of IL-6 and a negative correlation between PRL and sTNF RI was revealed. Quinagolide treatment may have a role in the management of SLE patients.

Prospective clinical study of writer's cramp.

Sixty-five consecutive patients with writer's cramp were studied prospectively to evaluate clinical and demographic features, the number of writing hours per day at dystonia onset, and the existence of trigger events. Assessment of writing and drawing was done on a standardized test using categorical scales. The importance of subjective handicap and pain, of postural and action tremor, the abnormal features of hand grip and the occurrence of mirror dystonia (dystonia occurring in the dominant hand when writing with the other hand) were studied. Thirty-two patients had simple writer's cramp, whereas the others had complex writer's cramp with several activities other than writing involved. No significant differences were seen in age of onset, legibility, pain, and handicap in these two groups. Seven patients had a family history of focal dystonia and six of them had a complex form of writer's cramp. Mirror dystonia was seen in 29 patients and in some it appeared useful to distinguish dystonic movements from secondary compensatory strategies.

Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations?

Autosomal dominant DOPA-responsive dystonia (DRD) is usually caused by mutation in the gene encoding guanosine triphosphate-cyclohydrolase I (GTPCH I). We studied 22 families with a phenotype of levodopa-responsive dystonia by sequencing the six coding exons, the 5'-untranslated region and the exon-intron boundaries of the GTPCH I gene. Eleven heterozygous mutations were identified, including five missense mutations, one splice site mutation, two small deletions and two nonsense mutations, in 12 families that included 27 patients and 13 asymptomatic carriers. Six mutations were new and five had already been reported. Four of the mutations caused truncation of the GTPCH I protein. One family carried a base-pair change in the 5'-untranslated region, not detected in controls, that could be responsible for the phenotype. Three of the remaining 10 families had deletions in the parkin gene on chromosome 6, underlining how difficult it is to distinguish, in some cases, between DRD and parkin mutations. No mutations were identified in seven families. The clinical spectrum extended from the classical DRD phenotype to parkinsonism with levodopa-induced dyskinesias, and included spastic paraplegia as well as the absence of dystonia.

Frequency of the DYT1 mutation in primary torsion dystonia without family history.

BACKGROUND: Idiopathic torsion dystonia is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 of the DYT1 gene was the first mutation found, in early-onset dystonia, with an autosomal dominant transmission and reduced penetrance. OBJECTIVE: To evaluate the frequency of the DYT1 mutation in patients with idiopathic torsion dystonia but without a family history. DESIGN: Prospective cohort study. SETTING: Four botulinum toxin clinics in the Paris, France, area. PATIENTS: A French population of 100 patients with dystonia. MAIN OUTCOME: Frequency of the DYT1 mutation tested by polymerase chain reaction and enzyme restriction analysis for the 946 GAG deletion, and genotype-to-phenotype correlation. RESULTS: Only 5 mutation carriers were identified, 4 of whom were part of a group of 10 patients with generalized dystonia. Onset was between ages 5 and 12 years as in typical early-onset dystonia. All 4 patients had cranial muscle involvement, which is atypical for DYT1 mutation carriers. One had segmental dystonia. Molecular analysis of relatives in 2 families demonstrated that the lack of family history was due to reduced penetrance. CONCLUSIONS: For accurate diagnosis and genetic counseling, screening for the DYT1 deletion is of great interest in cases with generalized dystonia without a family history. In other cases, positive results are rare.

Dopaminergic dysfunction in midbrain dystonia: anatomoclinical study using 3-dimensional magnetic resonance imaging and fluorodopa F 18 positron emission tomography.

OBJECTIVE: To determine the role of damage to neuronal systems, especially the dopaminergic system, in patients with symptomatic dystonia and mesencephalic lesions. DESIGN: Stereotaxic magnetic resonance imaging analysis and positron emission tomography after the administration of fluorodopa F 18. PATIENTS: Of a group of 48 patients with unilateral dystonia following a stroke, 7 patients with a well-defined midbrain lesion were selected. RESULTS: All patients had unilateral dystonic posture of an upper extremity and cerebellar dysmetria or hypotonia. Cerebellar tremor was present in 1 patient. Two patients had resting and postural tremor, which showed a marked improvement with treatment with levodopa. In patients with dystonia only, dopaminergic lesions were mostly confined to the ventromesial mesencephalon and red nucleus area, including the substantia nigra and nigrostriatal and cerebellothalamic fibers. Dystonia was severe and did not resolve with time in patients with lesions involving the nigrostriatal pathway, and the degree of dopaminergic denervation revealed by positron emission tomography was correlated with the severity of dystonia. In patients with resting and postural tremor, lesions of the dopaminergic structures were larger and located more laterally and dorsally in the pars compacta, the perirubral and retrorubral areas, and extending to the central tegmental tract. CONCLUSIONS: Dopaminergic dysfunction plays a role in the occurrence and severity of midbrain dystonia, and additional lesions to dopaminergic neurons in the perirubral and retrorubral areas result in tremor that responds to levodopa treatment.

DYT1 mutation in French families with idiopathic torsion dystonia.

A GAG deletion at position 946 in DYT1, one of the genes responsible for autosomal dominant idiopathic torsion dystonia (ITD), has recently been identified. We tested 24 families and six isolated cases with ITD and found 14 individuals from six French families who carried this mutation, indicating that 20% of the affected families carried the DYT1 mutation. Age at onset was always before 20 years (mean, 9+/-4 years). Interestingly, the site of onset was the upper limb in all but one patient. Dystonia was generalized in seven patients and remained focal or segmental in three patients. The absence of common haplotypes among DYT1 families suggests that at least six independent founder mutations have occurred. In addition, one Ashkenazi Jewish family carried the common haplotype described previously in Ashkenazi Jewish patients, but it was absent in the other family. Moreover, the dystonia remained focal in the latter family when compared with the usual generalized phenotype in patients with the common Ashkenazi Jewish haplotype. This indicates that there are at least two founder mutations in this population.

[Cerebral germ cell tumors in adults. A retrospective study of 19 cases]. / Les tumeurs germinales cérébrales de l'adulte. Etude rétrospective de 19 cas.

The authors report on the retrospective analysis of 19 patients with primary cerebral germ cell tumors which were treated between 1965 and 1993. Median age is 18 years (extremes: 16-55 years). There were 16 men and three women. The location of the primary tumor was the pineal area in six patients, suprasellar and hypothalamic area in five patients and other areas in eight patients. The histological pattern was non seminoma in six patients, dysgerminoma in eight; however no histological sample was obtained in five patients who did not have any particular characteristics (either cytological abnormalities or elevated tumor marker level). Three patients were treated by surgery only, eight patients received exclusive radiotherapy and eight patients had first line chemotherapy and further cranial irradiation. One was lost to follow-up. Six of eight assessable patients with dysgerminoma are alive with non evolutive disease (NED) after 15 to 176 month of follow-up. One out of five assessable patients with non seminomatous tumor in NED (163 month of follow-up). Finally all five patients who have no histological subtyping are alive with NED at 24 to 138 months. The standard treatment of dysgerminoma is currently first line chemotherapy followed by relatively low-dose and limited irradiation; the standard treatment of non-seminomatous cerebral germ cell tumor is chemotherapy, the study of which is warranted with the aim to decrease the toxicity and to increase the efficacy.

Thalamocortical diaschisis: positron emission tomography in humans.

To investigate further the relations between cortical energy metabolism and neuropsychological impairment after unilateral thalamic lesion, 55 patients underwent positron emission tomography studies of either cortical oxygen consumption or glucose utilisation, including eight repeat studies, at times ranging from 4 days to 98 months after the onset of the lesion [stroke (n = 44) or stereotaxic VL-Vim thalamotomy performed for movement disorders (n = 11)]. Patients with thalamotomy were also studied preoperatively and the surgery induced a significant fall in cortical metabolism on both sides (more so ipsilaterally); post-operatively the magnitude of the ipsilateral cortex hypometabolism was positively correlated to the severity of global neuropsychological impairment; similar but less significant findings were obtained for the ipsilateral/contralateral cortical metabolic asymmetry. With respect to the whole patient sample, the cortical metabolic asymmetry was initially pronounced, with subsequent monoexponential recovery, in the cognitively impaired study group, but it was only mild and showed no meaningful trend for recovery in the cognitively unaffected study group; yet even soon (< 3 months) after thalamic lesion there was a noticeable overlap of individual asymmetry values among the two study groups. These results lend further support to the view that the neuropsychological impairment that frequently follows unilateral thalamic lesions is reflected in a depression of synaptic activity in both the overlying and the contralateral cerebral cortices. For individual patients, this study also illustrates the potentially misleading nature of the measured cortical metabolic asymmetry with respect to neuropsychological status, especially at late times after lesion, in part because side to side metabolic ratios do not reflect bilateral changes.

Surgical treatment of prolactinomas. Short- and long-term results, prognostic factors.

All 347 patients surgically treated for a prolactinoma from January 1, 1976 to December 31, 1982, in the neurosurgical ward of Foch Hospital, were retrospectively studied. The frequency of postoperative normalisation of plasma prolactin (PRL) depends on prolactinoma size, preoperative PRL level, duration of first clinical symptom, previous oestroprogestative contraception, and adenoma necrosis. Postoperative PRL values were normalized in 75% of small prolactinomas (grade 0, 1 or 2) with preoperative PRL values less than 200 ng/ml, and clinical duration less than 5 years (n = 102). There was no operative death and minor morbidity (2.7%). Among the 96 patients with postoperative PRL normalisation, operated between 1976 and 1979, 70 were followed up for an average time of 4.4 +/- 0.2 years. 17% of patients had hyperprolactinemia recurrence with a delay of 1.5 +/- 0.4 years. Postoperative PRL levels near the upper normal limit, and weak PRL response to TRH tests were found to be unfavourable prognostic factors for hyperprolactinemia recurrence. Pregnancy did not increase the risk of recurrence, but could reflect genuine long-lasting remission. Selective adenomectomy remains an interesting treatment for prolactinoma, particularly if the adenoma is small, recent and with PRL moderately increased. The frequency of postoperative PRL normalisation after surgery is less than with bromocriptine, but surgery is the only treatment able to achieve a definitive cure with a low iatrogenic risk.

[Intention and action myoclonus disclosing occupational mercury poisoning]. / Myoclonies d'intention et d'action révélatrices d'une intoxication professionnelle par le mercure.

A 58-year-old laboratory-glassware manufacturer was referred to hospital because of coarse "tremor" of the upper extremities of 16-months-duration. Examination showed severe intention and action myoclonus, confirmed by electromyographic recording, slight memory impairment but was otherwise normal. Mercury levels were high in blood and urine (not in CSF) and, as other causes of myoclonus were excluded, inorganic mercury poisoning, was diagnosed. Only slight unilateral intention tremor persisted after dimercaprol treatment. Inhalation of mercury vapor was the mode of contamination. Myoclonus is the hallmark of severe inorganic mercury intoxication, the main clinical and pathological aspects of which are briefly discussed.