The tau gene A0 allele and progressive supranuclear palsy.

BACKGROUND: Recent studies have shown an association between a polymorphic tandem repeat allele, located in intron 9, of the tau gene and progressive supranuclear palsy (PSP). OBJECTIVE: To investigate this tau polymorphism in individuals with a clinical diagnosis of sporadic or familial PSP as well as in cases confirmed by pathology. METHODS: We analyzed the frequency of tau intronic polymorphism, the presence of linkage in two families with multiple cases of PSP, the splicing of exon 10, and direct sequence of the tau gene. RESULTS: We found that patients with a clinical diagnosis of sporadic or familial PSP and individuals with PSP confirmed by neuropathology have greater prevalence of the A0 allele and A0/A0 genotype than controls. This finding, however, was also true for asymptomatic relatives of individuals with PSP. Linkage analysis in familial PSP excluded the location of the gene in the region 17q21. Furthermore, no significant differences were found in the level of expression of exon 10 in PSP, A0/A0 brain with respect to Alzheimer A3/A3 brain. We found no mutations in the tau gene in individuals with familial PSP. CONCLUSIONS: A mutation in the tau gene was not the primary cause of familial PSP. The role of tau and the tau A0 allele in white PSP patients remains unknown, although it may represent a genetic risk factor for several neurodegenerative disorders.

Botulinum toxin treatment for spasmodic dysphonia: percutaneous versus transoral approach.

Spasmodic dysphonia (SD) is at present defined as focal dystonia. Botulinum toxin (BT) injection is the treatment of choice for SD. BT is usually injected by a percutaneous route, but a direct, visually guided transoral approach has also been successful. It is not known whether percutaneous injection is as effective as the transoral approach. This article reviews our experience with both techniques of injection on 29 patients with adductor type SD. Since 1992, we have carried out 48 treatment sessions with the transoral technique and 76 treatment sessions with the percutaneous technique. Two patients did not respond to the percutaneous technique despite several attempts, but they did respond to the transoral approach. Globally, transoral technique was superior to percutaneous technique in terms of effectiveness (48 of 48 responses with transoral technique versus 61 of 76 responses with percutaneous approach, p < 0.01). Dosage of BT, duration, and side effects were similar with both techniques. This article also describes a simple, inexpensive device, composed of materials on hand at every hospital, that facilitates the transoral approach.

[Laryngeal dystonia. Comparison of transcutaneous and transoral injection of botulinum toxin]. / Distonía laríngea. Tratamiento con toxina botulínica mediante técnica transcutánea y transoral. Estudio comparativo.

Spasmodic dysphonia is a focal dystonia that effects the proximal muscles (adduction dystonia) or dilatory (abduction dystonia) of the larynx. Botulinum toxin (BTX), generally delivered by percutaneous injection, is the treatment of choice. Recently, use has been made of a transoral route of delivery, with BTX injected through a curved device with visual control. It remains to be determined which route is better. Percutaneous injection is simple and well-tolerated, but the transoral route is theoretically more effective. We assessed the efficacy of both techniques in 19 patients with adduction dystonia, conducting 55 treatment sessions by percutaneous injection and 20 by transoral injection. All the transoral treatments were effective (20/20, 100%), but only 81% (45-155) of the percutaneous treatments were (p < 0.05). Two patients who had doubtful responses after percutaneous delivery improved considerably when the transoral approach was used. In spite of its greater complexity, the transoral approach is probably more effective than the percutaneous route. We describe a curved device for transoral injection that is composed of simple elements available at any health center.

Somatic stability in chorionic villi samples and other Huntington fetal tissues.

We have studied different tissues from two affected fetuses with Huntington's disease (HD). In the first case the analysis was performed at 11 weeks of pregnancy; CAG repeats from seven different tissues were compared with the results obtained in the chorionic villi sample (CVS). We found 42 CAG repeats in all samples. In the second case the study was done at 12 weeks; eight tissues (including brain) were studied and compared with the CVS; in all of them, 44 CAG repeats were obtained. Our results show a somatic stability in the different analyzed tissues and suggest that mitotic instability can be a secondary consequence of neuronal degeneration and gliosis. Likewise, our data show great viability in the prenatal diagnosis (PD) of Huntington's disease using samples from any tissue.

Huntington's disease: a multidisciplinary study.

Huntington's disease (HD) is characterized by the presence of movement disorders, cognitive decline and psychiatric disturbances. Recently, the gene responsible for HD has been found. As a result, a more direct test for HD is available. This may lead to a comprehensive approach to HD, since it is now possible to study HD patients without uncertainties in diagnosis. We carried out a clinical-genetic study on 45 patients with HD. We performed molecular analysis on 39 patients. All had an abnormal expansion of (CAG)n ranging from 41 to 90 triplets (mean 50.8 ± 11.5 S.D.). There was a strong inverse correlation between (CAG)n expansion and age at onset Gender of the affected parent influenced age at onset (p < 0.001) and number of triplets (p < 0.001). A significant impairment of akinesia (p < 0.001), chorea (p < 0.005), MMSE (p < 0.01) and Rey scores (p < 0.05) occurred across successive stages of functional disability. Hooper Visual Organization Test (HVOT) scores did not change significantly across stages, but this test was extremely useful to discriminate between patients at an early stage and controls. A significant correlation was found between functional disability and motor-cognitive decline; correlation was stronger for motor (akinesia, r = 0.77; chorea, r = 0.61) than for cognitive aspects (MMSE, r = - 0.54; Rey, r = - 0.51; HVOT, r = -0.35).

Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease.

In this study, the effects of a diet rich in insoluble fiber (DRIF) on motor disability and the peripheral pharmacokinetics of orally administered L-dopa in Parkinsonian patients with marked constipation are analyzed. We found a useful effect of a DRIF on plasma L-dopa concentration and motor function. The greatest effect on the plasma L-dopa levels was found early (at 30 and 60 min) after oral administration. There was a relationship between the improvement of constipation and the higher bioavailability of L-dopa. DRIF can be a coadjuvant treatment in patients with Parkinson's disease.

[Craniocervical dystonia and facial hemispasm: clinical and pharmacological characteristics of 52 patients]. / Distonía craneocervical y hemiespasmo facial: características clínicas y farmacológicas de 52 enfermos.

The results obtained in a retrospective study on clinical and pharmacological aspects of 41 patients suffering craniocervical dystonia (24 with blepharospasm, 17 with torticollis) and 11 with spasm are here presented. Mean age of symptoms onset was 57.4, 43.8 and 55.8 years old respectively; this variable was comparatively higher in females than in males with torticollis. The prevalence of blepharospasm and hemifacial spasm was higher in females. A 38.7% of patients suffering blepharospasm also presented oromandibular dystonia (Meige's syndrome). Other abnormal movements less frequently associated were cephalic tremor, postural hand tremor and larynx dystonia. In three cases with blepharospasm there was family history of Parkinson's disease and in two cases with torticollis there was family history of essential tremor. The mean age of onset was lower in patients with clonic torticollis and the evolution time of symptoms was longer than in those who presented the tonic type. Clonic torticollis were less frequently associated to pain. Trihexyphenidyl (anticholinergic) was the most efficient drug in craniocervical dystonia, and clonazepam in facial hemispasm. In general, as earliest the age of onset was, as better the therapeutical response was.

[Focal dystonias and facial hemispasm: treatment with botulinum A toxin]. / Distonías focales y hemiespasmo facial: tratamiento con toxina botulínica A.

We report the results of the treatment of 80 patients with various idiopathic focal dystonia and essential hemifacial spasm with Botulinum A toxin. A statistically significant improvement was obtained in our 34 patients with blepharospasm, 19 patients with hemifacial spasm, 59% of 22 patients with cervical dystonia and 60% of 5 patients with hand dystonia. Mean duration of the benefit of each injection was 15.3, 16.3, 7.6 and 8.7 weeks respectively. Adverse effects were local and transient. We concluded that botulinum A toxin is a safe and effective therapy for patients with focal dystonia and hemifacial spasm.

[Physiopathology of dystonia]. / Fisiopatología de la distonía.

Dystonia is a movement disorder characterized by sustained twisting movements and muscle contractions and abnormal postures. Dystonia is a symptom present in many diseases of the central nervous system. Anatomical data reveal that dystonia appears in diseases involving the basal ganglia, diencephalon, brain stem and cerebellum. Physiological studies revealed an abnormal facilitation of polysynaptic reflexes at the brain stem level. A common pathogenic mechanism for dystonia must be found in order to delineate in effective treatment. From clinical and biochemical data we suggest that dystonia is produced by abnormal shift to the norepinephrine/dopamine neurotransmission in favor of norepinephrine in different brain areas.

Differential expression of neurofilament triplet proteins in carcinoid tumours: an immunohistochemical study.

Neurofilaments (NFs) are specific intermediate filaments to neural cells. Mammalian NFs are protein triplets composed of three major subunits with respective molecular weights of approximately 70, 150 and 200 kD. Using an immunohistochemical method, 13 carcinoid tumours from different sites were examined for the presence of these three subunits by means of monospecific antisera. All tumours contained cells that were positive for the 70 Kd subunit; nine cases contained cells immunoreactive for the 150 Kd subunit and only three of them for the 200 kD subunit. The results indicate that the 70 kD subunit is a good overall marker of carcinoid tumours. The 150 and 200 kD subunits are more likely to be absent in carcinoids, both typical and atypical.

[Focal dystonias and facial hemispasm: treatment with botulinum A toxin]. / Distonías focales y hemiespasmo facial: tratamiento con toxina botulínica A.

We report the results of the treatment of 80 patients with various idiopathic focal dystonia and essential hemifacial spasm with Botulinum A toxin. A statistically significant improvement was obtained in our 34 patients with blepharospasm, 19 patients with hemifacial spasm, 59% of 22 patients with cervical dystonia and 60% of 5 patients with hand dystonia. Mean duration of the benefit of each injection was 15.3, 16.3, 7.6 and 8.7 weeks respectively. Adverse effects were local and transient. We concluded that botulinum A toxin is a safe and effective therapy for patients with focal dystonia and hemifacial spasm.

[Physiopathology of dystonia]. / Fisiopatología de la distonía.

Dystonia is a movement disorder characterized by sustained twisting movements and muscle contractions and abnormal postures. Dystonia is a symptom present in many diseases of the central nervous system. Anatomical data reveal that dystonia appears in diseases involving the basal ganglia, diencephalon, brain stem and cerebellum. Physiological studies revealed an abnormal facilitation of polysynaptic reflexes at the brain stem level. A common pathogenic mechanism for dystonia must be found in order to delineate in effective treatment. From clinical and biochemical data we suggest that dystonia is produced by abnormal shift of the norepinephrine/dopamine neurotransmission in favor of norepinephrine in different brain areas.

[Clinical and epidemiologic characteristics of familial Parkinson disease]. / Características clínicas y epidemiológicas de la enfermedad de Parkinson familiar.

We have studied 44 patients diagnosed of idiopathic Parkinson disease included in our database of rigid-akinetic syndromes. We have compared their demographic, environmental and clinical features with the ones that presented a group on 22 patients diagnosed of idiopathic Parkinson disease and had some first degree relatives with the same disease. Patients with familial Parkinson disease are distinguished from the ones that suffer from sporadic Parkinson disease because of an early start, greater consanguinity rate and greater frequency of a similar disease in their parents. Moreover, we have seen that familial Parkinson disease patients have drunk more water from wells during their lives than the ones that suffer sporadic Parkinson disease, present greater frequency of wide motoricity disorders, dystonia, night hypokinesia, fluctuations in relation to L-DOPA and greater frequency of early going grey. We have not found either epidemiologic data which could explain the appearance of familial cases or environmental causes which could produce familial Parkinson disease. Clinical differences between the two groups are likely due to an early start of symptoms in familial Parkinson disease cases. According to our data we could not conclude that between familial and sporadic Parkinson disease are significant differences in to justify two well-defined diseases. Even, the familial presentation of idiopathic Parkinson disease could be the normal form of Parkinson disease if long survival was a favourable factor of disease onset in pre-symptomatic persons.

[Reflex sympathetic dystrophy. A new manifestation of Lyme disease?]. / Distrofia simpática refleja. Nueva manifestación de la enfermedad de Lyme?

Several syndromes derived from the involvement of central and peripheral nervous system and meninges have been reported in the infection by Borrelia burgdorferi. The features of autonomic nervous system involvement have received a marginal attention. Reflex sympathetic dystrophy is an autonomic picture characterized by regional sympathetic hyperactivity which has not been associated with Lyme disease. We report a 16-year-old female with clinical, radiological and scintigraphic features consistent with reflex sympathetic dystrophy. The usual causes of this syndrome were ruled out and antibodies against Borrelia burgdorferi were detected by immunofluorescence, enzyme immunoassay and Western blotting. Specific IgG and IgM levels had a progressive increase during three months. In Lyme borreliosis causes of false positives were excluded. Antigen-antibody bands were detected in increasing number during the evolution, using sonicates of B. burgdorferi and patient's sera with the Western blotting technique. Our data suggest that reflex sympathetic dystrophy is another type of nervous system involvement in the multifaceted Lyme borreliosis.