Pelvic dyskinesia with an outstanding response to tetrabenazine.

We report on a patient who presented an invalidating progressive pelvic dyskinesia while receiving different kinds of neuroleptic drugs for a psychiatric disorder. The clinical features and different drug-induced movement scales showed an outstanding improvement after tetrabenazine was started. To the best of our knowledge, this is the first case report of pelvic dyskinesia with good evolution and control of dyskinesias after treatment with tetrabenazine.

Electrophysiological study of ephaptic axono-axonal responses in hemifacial spasm.

One of the classic features of hemifacial spasm (HFS) is spread of the blink reflex responses to muscles other than the orbicularis oculi. The pathophysiological mechanisms underlying the generation of such abnormal responses include lateral spread of activity between neighboring fibers of the facial nerve and hyperexcitability of facial motoneurons. In this report we present evidence for another mechanism that can contribute to the generation of responses in lower facial muscles resembling the R1 response of the blink reflex. In 13 HFS patients, we studied the responses induced in orbicularis oris by electrical stimuli applied at various sites between the supraorbital and zygomatic areas. We identified responses with two different components: an early and very stable component, with an onset latency ranging from 10.5 to 14.8 ms, and a more irregular longer-latency component. Displacement of the stimulation site away from the supraorbital nerve and towards the extracranial origin of the facial nerve caused a progressive shortening of response latency. These features indicate that, in our patients, the shortest latency component of the orbicularis oris response was likely generated by antidromic conduction in facial nerve motor axons followed by axono-axonal activation of the fibers innervating the lower facial muscles. Our results suggest that motor axono-axonal responses are generated by stimulation of facial nerve terminals in HFS.

Lymphocyte populations in Parkinson's disease and in rat models of parkinsonism.

To assess the involvement of the immune system in Parkinson's disease we studied the phenotype of circulating lymphocytes in 30 untreated and 34 treated patients. We found a numeric decrease in helper T cells (higher in CD4(+)CD45RA(+) than in CD4(+)CD29(+)) and B cells, and a rise in activated, CD4(+)CD25(+) lymphocytes that was correlated with lymphocyte depletion. All these alterations were independent of levodopa treatment. In addition, we performed striatal dopamine depletion in rats with either MPP(+) or 6-OHDA, showing that MPP(+) but not 6-OHDA can increase CD4(+)CD25(+) lymphocytes. Thus, mechanisms other than dopamine deficit may explain the immune activation in Parkinson's disease.

Significant changes in the tau A0 and A3 alleles in progressive supranuclear palsy and improved genotyping by silver detection.

BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by intraneuronal inclusions of neurofibrillary tangles formed by aggregated tau protein. A significant association between the tau gene A0/A0 genotype and PSP recently has been reported. OBJECTIVES: To determine if a significant association between the tau gene A0/A0 genotype and PSP could be found in an independent population with a genetic background different from that in which the initial association was reported, and to standardize a nonradioactive method for tau gene genotyping. SETTING: Hospital and university research laboratories. SUBJECTS AND METHODS: To facilitate genotyping of the tau gene, we standardized the conditions for silver-based detection of the tau gene dinucleotide polymorphism. Thirty patients from Spain clinically diagnosed as having probable PSP were included in the study and compared with different control groups. RESULTS: A highly significant overrepresentation of the A0/A0 genotype (P<.001) and a decrease in the frequency of the A0/A3 genotype were found in the Spanish patients with PSP compared with the control group. A method based on silver detection was standardized for the genotyping of the tau gene. CONCLUSIONS: The detection of a significant association between the tau gene A0/A0 genotype and PSP in 2 independent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 genotype is a risk factor for developing PSP independent of genetic background. Alternatively, the results could be interpreted as a protective effect of the A3 allele.

[Molecular analysis of the IT15 gene in 79 Spanish families with Huntington's disease: diagnostic confirmation and presymptomatic diagnosis]. / Análisis molecular del gen IT15 en 79 familias españolas afectadas de enfermedad de Huntington: confirmación diagnóstica y diagnóstico presintomático.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder with late age of onset, caused by (CAG), expansion in the IT15 gene. We present here the results of IT15 gene study in Spanish families in order to show the usefulness of diagnosis, genetic counseling and clinical-genetic correlation in Spanish population. PATIENTS AND METHODS: We have studied the number of (CAG)n repeats in the IT15 gene by PCR analysis in 137 individuals from 79 Spanish families with HD. RESULTS: The number of (CAG)n repeats in HD chromosomes varied from 35 to 85, while the range for the normal chromosomes was from 13 to 31. In four juvenile cases the number of (CAG)n repeats was above 50. In three of these cases the transmission was paternal. The (CAG)n expansion was demonstrated in 98.3% of the cases. We established the diagnosis in 15 uncertain clinical diagnosis. We made a presymptomatic diagnosis after psychological-psychiatric evaluation in 50 HD at risk individuals. We showed an inverse correlation between the number of (CAG)n repeats and the age at onset of the disease. CONCLUSIONS: The (CAG)n repeats study in the IT15 gene in Spanish populations allows the confirmation of diagnosis of HD as well as presymptomatic testing enabling the genetic counseling. There is an inverse correlation between the age of onset of the disease and the number of (CAG)n repeats in the IT15 gene.

[Bilateral asymmetric degeneration of the striatum as a cause of senile hemiballism]. / Degeneración bilateral y asimétrica del estriado como causa de hemibalismo senil.

We report the case of an 82-years old woman with sporadic acute hemiballism associated with bilateral striatal degeneration of non vascular origin which was most severe in the side contralateral to the hemiballism. The patient's neuropathological lesions resembled those of patients with senile chorea. Although hemiballism has never been described as an isolated manifestation of primary degeneration of the striatum, it may so occur in elderly patients with hemiballism.

Huntington's disease: confirmation of diagnosis and presymptomatic testing in Spanish families by genetic analysis.

Huntington's disease is a neuropsychiatric disorder with late age of onset, caused by an elongation of a (CAG)n repeat in the IT15 gene. This trinucleotide repeat has been studied by polymerase chain reaction amplification in 86 members of 43 Spanish families with Huntington's disease and in 60 unrelated subjects from the general population. The number of (CAG)n repeats in Huntington's disease chromosomes varied from 40 to 85, with 49 and 52 repeats being the most common, whereas in normal chromosomes it ranged from 12 to 32 with 20 (CAG)n repeats being the most frequent allele. In four patients with juvenile onset the number of (CAG)n repeats was greater than 50 and only one was of maternal transmission. There was a clear inverse correlation between the number of repeats and the age of onset of the disease. The study contributed to the diagnosis of 10 patients in whom the clinical diagnosis was uncertain, and identified 41 "at risk" patients after a previous psychological-psychiatric evaluation.

T cell subsets in multiple sclerosis: a serial study.

The relevance of abnormalities in the distribution of peripheral blood T lymphocyte subsets to the clinical manifestations of multiple sclerosis is not firmly established. A clinical and immunological follow-up of relapsing-remitting multiple sclerosis patients was performed in order to study the relationship of immune changes with the clinical course of the disease. Twenty patients were monitored monthly during a mean time of nine months for peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19), including the immunoregulatory subsets CD4CD29 (helper-inducer), and CD4CD25) by flow cytometry. A total of 14 untreated relapses was included. The most significant observations were a decrease in T suppressor-inducer CD4+ CD45RA+ subset during clinical relapses (P = 0.028) that was also detectable one month before (P = 0.020) and the lack of changes in CD4+ CD29+ and CD8+ T cells. In addition, variations in the percentage of CD4+ CD25+ activated T helper cells were not associated with clinical exacerbations. These results indicate the existence of a temporal association of immune changes in peripheral blood, but not activation, with the clinical manifestations of multiple sclerosis.

Cerebrospinal dopamine metabolites in rats after intrastriatal administration of 6-hydroxydopamine or 1-methyl-4-phenylpyridinium ion.

Dopamine (DA) and its main cerebral metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in striatum and cerebrospinal fluid (CSF) from cisterna magna in rats bilaterally lesioned by intrastriatal administration of 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium ion (MPP+). 6-OHDA caused a progressive lesion in striatum that is only moderately reflected in the decrease in dopamine metabolite concentration in CSF. MPP+ caused an acute but less selective lesion in the dopamine striatal system, as indicated by a significant reduction in striatal GABA content, followed by a slow recovery in dopamine striatal metabolism and content. The locomotor activity was dramatically reduced in both groups 48 hours after the treatment but remained significantly decreased after two months only in 6-OHDA lesioned animals. A positive correlation was found between HVA CSF concentration and striatal DA content in MPP+ lesioned rats, but not in 6-OHDA lesioned rats. It is concluded that the concentration of dopamine metabolites in CSF can be altered only after a severe striatal lesion: reduction of striatal dopamine content below 50% of normal values and involvement of neuronal or non-neuronal elements other than the dopaminergic system, similarly to the lesions caused by MPP+. These results may partly explain why CSF dopamine metabolites concentrations were significantly decreased both in advanced stages of parkinsonism and in other neurodegenerative disorders.

CSF somatostatin increase in patients with early parkinsonian syndrome.

Somatostatin-like immunoreactivity levels (SLI) in cerebrospinal fluid (CSF) were determined in twenty-three patients with untreated parkinsonian syndrome (15 with Idiopathic Parkinson's disease (IPD) and 8 with other forms of parkinsonism) at the moment of clinical diagnosis (mean duration of disease 1.1 +/- 0.2 years), and in 26 subjects without neurological symptoms. None of the IPD patients had a diagnosis of dementia at the moment of inclusion in the study. CSF-SLI content was found to be significantly higher in patients with parkinsonian syndrome (107.9 +/- 9.8 pg/ml) than in control subjects (73.5 +/- 8.4 pg/ml). The increase was also significant when controls were compared with IPD patients. In addition, a positive correlation between SLI and homovanillic acid was found in CSF of all patients. A test of learning memory was used to evaluate the mental state of patients and a significant increase in CSF-somatostatin levels was observed in patients with Idiopathic Parkinson's disease and severe affectation of memory. These results indicate that in the early steps of untreated parkinsonian syndrome, somatostatin concentration in cerebrospinal fluid may increase, probably due to the neurodegenerative depletion of somatostatin from striatal or cortical neurons.

Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) decreases striatal fructose 2,6-bisphosphate in rats.

The stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP+ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP+ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2,6-bisphosphate recovery. The stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP+. On the other hand, they show that MPP+ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondrial chain blockage.

Cerebrospinal monoamine metabolites and amino acid content in patients with parkinsonian syndrome and rats lesioned with MPP+.

Monoamine metabolites and amino acid concentration in cerebrospinal fluid (CSF) of 33 untreated patients with parkinsonian syndrome, and 20 control patients without specific neurological symptoms have been compared with those obtained in cerebrospinal fluid of rats intrastriatally lesioned with 1-methyl-4-phenylpyridinium ion (MPP+) and sham operated animals. Homovanillic acid content was found to be significantly lower in patients with severe parkinsonism (motor score of UPDRS > 24), but not in patients with mild symptoms (motor score < or = 24). A correlation between the loss of striatal dopamine and the decrease in cerebrospinal homovanillic acid has been established in rats treated with MPP+. The extrapolation of these results to those obtained from human patients could be important in assessing the degree of striatal dopamine loss shown by humans with parkinsonian syndrome at the moment of clinical diagnosis. No significant differences were found between the other monoamine metabolites analyzed and free amino acid content in human and rat CSF.

Bilateral striatal lesions in childhood.

From 1983 to 1991, 13 patients were identified with a clinical radiologic association characterized by acute or persistent neurologic dysfunction and bilateral lesions in the basal ganglia region demonstrated by ultrasound, computed tomography, or magnetic resonance imaging. Initial clinical manifestations of this group of patients were characterized by extrapyramidal signs (i.e., dystonia 9, hypotonia 2, athetosis 1, rigidity 1), altered state of consciousness in 5, and seizures in 3. The outcomes of most of these patients were poor: 10 had motor sequelae, 9 cognitive impairment, and 4 died. The outcomes of 2 patients, however, were much better than what was expected from the initial presentation. Based on current and previous reports, the diagnostic approach and classification of patients with neurologic dysfunction and bilateral striatal lesions are presented.

[Polymicrogyria and ulegyria. Diagnosis by magnetic resonance]. / Polimicrogiria y ulegiria. Diagnóstico por resonancia magnética.

Three patients who had had epilepsy since the second decade of life were studied with cranial magnetic resonance (MR). Two patients had no antecedents of interest during pregnancy and the perinatal period and neurological examination was normal. The third patient had had dystocia and presented left hemiparesia since then, with normal intellectual development. None of the cases had any family history of neurological disease. Cranial magnetic resonance was performed in the three patients demonstrating polymicrogyria in two and ulegyria in the other, in addition to other lesions. The first patient presented an unilateral area of polymicrogyria related with a porencephalic cyst in the distal territory of the right sylvian artery and ipsilateral heterotopia of periventricular location. The second patient presented bilateral periventricular heterotopia, partial agenesis of the corpus callosum and an enlarged cisterna magna in addition to bilateral frontal-occipital polymicrogyria. Finally, ulegyria was observed in the third patient in the edges and neighboring regions of a right rolandic porencephalic cyst, as well as an enlarged cisterna magna.

[Magnetic resonance imaging and Cogan's syndrome]. / Imagerie par résonance magnétique et syndrome de Cogan.

We report the case of a 25-year old man with vestibulocochlear and ocular impairment compatible with Cogan's syndrome. Later on, severe headache developed. CT scan showed an ischaemic lesion in the right frontal lobe. Magnetic resonance imaging demonstrated multiple bilateral nodular lesions on T2-weighted sequences. These were unmodified at a second MRI examination performed six months later. Under corticosteroids, the neurological and ophthalmic symptoms disappeared, but the patient remained deaf. We believe that this patient had vasculitis involving the brain, with infarcts. To our knowledge, no case of Cogan's syndrome with cerebral magnetic resonance imaging has yet been reported.

Giant basilar aneurysm in the course of subacute bacterial endocarditis.

We describe a man aged 42 years with mitral valve regurgitation who suffered from subacute bacterial endocarditis caused by Streptococcus morbillorum. The clinical picture began with a toxic syndrome. Five months later, the patient had an embolic episode and a right rostral pontine stroke, which was followed a few days later by an adversive focal seizure on the right. Despite antibiotic treatment, he suffered complete third nerve palsy. Arteriography, magnetic resonance imaging, and computed tomography of the brain showed a giant aneurysm in the rostral end of the basilar artery; the aneurysm was clipped. We discuss the clinical features, radiology, and characteristics of this aneurysm as a unique case of a giant bacterial aneurysm in the vertebrobasilar system.

Formation and growth of the cerebral convolutions. II. Cell death in the gyrus suprasylvius and adjoining sulci in the cat.

Cell death, calculated by counting pyknotic nuclei to assess the number of dying cells, in the gyrus suprasylvius (GS-Syl) and adjoining sulci sulcus lateralis (SL) and sulcus suprasylvius (SS-Syl) was studied in cats aged 5, 15, 25 days and 6 months. Three patterns of cell death were characterized: (1) an ascending gradient from the inner to the upper cortical layers; (2) a lateromedial gradient from the SS-Syl towards the SL; and (3) a predominance of cell death in the sulcal zones. These patterns are in accordance with the sequence of cortical neurogenesis, the lateromedial pattern of the whole formation and growth of the GS-Syl and adjoining sulci, and the differences in the cortical thickness between the sulci and the gyral crown.