A kindred with cerebellar ataxia and thermoanalgesia.

OBJECTIVE: To characterise the clinical, neurophysiological, neuropathological and genetic features of a family with cerebellar autosomal dominant ataxia. DESIGN: Patients were submitted to clinical, neuroradiological and neurophysiological examinations. Molecular studies were undertaken to exclude SCAs 1-3, 6-8, 12 and 17. Studies were performed to rule out linkage to SCA4 on chromosome 16, and for all still uncharacterised SCA loci. Neuropathological examination of the proband was performed with immunocytochemistry. RESULTS: These patients presented a late onset cerebellar ataxia with thermoanalgesia and deep sensory loss. Unlike in SCA4, reflexes were preserved. MRI revealed cerebellar, medullar and spinal cord atrophy. Neurophysiological studies showed absence or marked reduction of the sensory nerve action potentials and somatosensory evoked potentials in lower and upper limbs but preservation of the soleus H reflex. No triplet repeat expansion mutations in the studied SCA genes were identified. Our studies ruled out linkage of the disease to the SCA4 locus on chromosome 16 and the remaining reported SCA loci. The neuropathological study of the proband revealed severe loss of Purkinje cells and dentate neurons. The inferior olive and lower cranial nerve nuclei also showed extensive cell loss. Posterior columns and spinocerebellar tracts were demyelinated. Ubiquitin immunoreactive intranuclear inclusions were absent. CONCLUSION: This kind of cerebellar ataxia, associated with thermoanalgesia as well as deep sensory loss with retained reflexes, does not associate to any known SCA loci. Therefore, we identify and describe a new form of late onset dominant spinocerebellar ataxia.

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (P<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

Deteriorating ischemic stroke: risk factors and prognosis.

To determine a risk profile of deterioration in cerebral infarction of less than 8 hours' duration, we studied prospectively a series of clinical and radiologic data in 98 patients. We evaluated the Canadian Neurological Scale Score and Barthel index during a follow-up period of 3 months. There was deterioration in the 1st 48 hours in 40.8% of the patients. High systolic blood pressure, elevated blood sugar concentration at admission, and carotid territory involvement were independently related with deterioration in the logistic regression analysis. Death occurred in 35% of the patients with deteriorating infarcts and in 8.6% of those with stable infarcts. At the end of the study, functional capacity was lower in those with deteriorating infarcts, but the 2 groups improved in parallel from the 4th day onward.

Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms.

We report the clinical, neuropathologic, and genetic studies of a large kindred (family M-ADCA1) with autosomal dominant spinocerebellar ataxia type 1 (SCA1), ascertained in 41 members, with clinical data available in twenty-two. The mean age of onset was 36.3 +/- 6.2 years (ages, 26 to 52), the mean duration of the disease was 15.8 +/- 6.5 years (range, 10 to 28 years), and the mean age at death was 54.1 +/- 9.5 years (ages, 39 to 72). Premonitory signs and symptoms appeared earlier than the usual onset symptoms in many of the clinically unaffected patients who inherited the mutated SCA1 gene. Anticipation was present when we compared the seventh and eighth generations. A more severe course of the disease occurred in offspring of affected males. Neuropathologic examination, performed on three patients, showed the usual findings of SCA1; Golgi and immunocytochemistry studies suggested primary damage of the Purkinje cells. We analyzed the CAG-repeat mutation responsible for the SCA1 phenotype in a total of 41 family members. There was expansion in 19 subjects (10 clinically affected, seven with early signs and symptoms, and two asymptomatic individuals), and all showed heterozygosity, with one allele between 41 and 59 repeats (SCA1 mutation) and the other in the range of 6 to 39 repeats (normal range). The clinical analysis of "at risk" patients with the SCA1 mutation showed that minor signs and symptoms begin before full clinical diagnosis, and these premonitory manifestations can herald full development of SCA1 by years.

Balint's syndrome. Report of four cases with watershed parieto-occipital lesions from vertebrobasilar ischemia or systemic hypotension.

Four patients with Balint's syndrome secondary to bilateral parieto-occipital ischemic lesions are presented. The pathogenesis of these lesions corresponded to either occlusive arterial disease in the vertebro-basilar system or the effects of systemic hypotension. The clinical features of this syndrome are discussed, along with the pathophysiology and time course of the condition, with particular emphasis on etiological factors, which make of this condition a distinct clinico-pathological syndrome.

[Value of the transcranial Doppler examination in the diagnosis of brain death]. / Valor del examen Doppler transcraneal en el diagnóstico de la muerte cerebral.

BACKGROUND: Transcranial Doppler examination (TCD) is a non invasive method capable of detecting the interruption of cerebral flow in patients with criteria of brain death. Its recognition as an alternative to isoelectric EEG for the diagnosis of brain death requires previous validation. METHODS: Twenty-six patients in profound coma were examined by TCD. Of 23 patients with technically adequate study 13 manifested clinical criteria and EEG of brain death. Of these patients 9 had received barbiturate treatment and 4 had not. RESULTS: Changes in the flow waves of the TCD were observed in the form of diastolic reflux or systolic points of slight amplitude without diastolic flow in at least 2 arteries in 12 of 13 patients with criteria of brain death (sensitivity = 92%) and in none of the 10 patients without criteria of brain death (specificity = 100%). The use of barbiturates did not modify the normal anterograde flow detected by TCD in the absence of criteria of brain death. CONCLUSIONS: Transcranial Doppler is a good method for confirming the clinical diagnosis of brain death, fundamentally in patients undergoing treatment with drugs depressing the central nervous system.

[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.