Giuseppe Campanella

Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy.

SummaryAn epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10−5 inhabitants (95% confidence limits 4.8–11.1). There were 7 patients with Friedreichs disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia.

Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients

SummaryThe clinical and genetic features of 80 patients with Friedreichs disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6–9 and 12–15 years. Analysis of intrafamily variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease.

Dopamine D1 and D2 receptors mediate opposite functions in seizures induced by lithium-pilocarpine

The effect of selective dopamine receptor blockade on epileptic activity was tested in rats, using the lithium-pilocarpine seizure model. One day after lithium pretreatment, systemic administration of the dopamine D1 antagonist, SCH 23390, prevented the convulsive activity induced by either 10 or 15 mg/kg of pilocarpine in a dose-dependent manner as revealed by behavioral and electroencephalographic alterations. No anticonvulsant effect was observed when SCH 23390 was injected at the same time as lithium and 24 h prior to pilocarpine. Furthermore, the D2 antagonists, raclopride and haloperidol, potently reduced the threshold for convulsions induced by 10 mg/kg of pilocarpine, following lithium pretreatment. Neither dopamine D1 nor D2 antagonists altered the limbic stereotypies induced by pilocarpine, supporting the view that the dopamine system is primarily involved in the mechanisms of convulsion generation and seizure spreading. These results indicate that dopamine receptor subtypes exert opposite functions on the regulation of convulsive activity.

Has spinocerebellar ataxia type 2 a distinct phenotype? Genetic and clinical study of an Italian family

Article abstract-The gene for spinocerebellar ataxia type 2 (SCA2) is mapped to chromosome 12q23-24.1. Using D12S79 and D12S105, we performed linkage analysis in nine individuals including six affected members of a four-generation family in which we excluded SCA1 by direct mutation analysis. We obtained a lod score = 2.37 at theta = 0.00 for the compound haplotype. The clinical picture appeared homogeneous, showing the absence of corticospinal signs and the presence of peripheral neuropathy. The present study suggests that this SCA2 family is clinically different from most SCA1 families. NEUROLOGY 1995;45: 793-796

Age of onset, sex, and cardiomyopathy as predictors of disability and survival in Friedreich's disease: A retrospective study on 119 patients

We performed a retrospective study on a series of 119 of our patients who have Friedreichs disease to assess the predictive value of age at onset, gender, and left ventricular hypertrophy in regard to disease progression.Outcome variables were survival, time to loss of independent gait, and time to confinement in a wheelchair. Diabetes was considered to be an outcome variable when defining time to diabetes and an explanatory variable when testing its effect on survival. Eleven patients died. The median estimated survival from onset was 36 years, and the median time to loss of independent gait was 8 years and to confinement in a wheelchair was 15 years from onset. Nineteen patients developed diabetes after a median time of 16 years. The presence of left ventricular hypertrophy or diabetes significantly reduced survival based on univariate analysis. Onset at the age of <or=to20 years and the presence of left ventricular hypertrophy predicted a faster rate of progression of the disease. NEUROLOGY 1996;47: 1260-1264

Clinical and genetic heterogeneity in early onset cerebellar ataxia with retained tendon reflexes.

A clinical and genetic study was performed on 20 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Mean age at onset was 8.8 (SD 6.0) years. The frequency distribution of age of onset significantly differed from the normal distribution. Consanguinity rate was 16.7% and segregation ratio 0.164. As well as ataxia, which was a constant feature, there were signs of involvement of the cortico-spinal tracts and/or peripheral nerves in most patients. Results of neurophysiological studies were not homogeneous, nor were morphological findings of the sural nerve biopsy. The data suggest that EOCA may be genetically and clinically heterogeneous.

Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes

We studied 83 patients from 36 Italian families with autosomal dominant cerebellar ataxia type I. Mean onset age +/- SD was 34.2 +/- 12.8 years with a mean anticipation of 12.8 +/- 15.1 in 52 parent-offspring pairs. Onset age anticipation occurred predominantly through paternal transmission. Mean age at death was at 56.5 +/- 15.5 years. The most common associated features were supranuclear ophthalmoplegia, corticospinal signs, peripheral neuropathy and cognitive impairment. Cerebellar atrophy was constant at MRI and usually associated with shrinkage of the pons and degeneration of the pontine transverse fibres. Direct mutation analysis in 29 families showed two families with SCA1 and none with Machado-Joseph/SCA3 mutation. We performed linkage analysis in the ten largest families. Two of them showed linkage to SCA2 locus and none to SCA4 and SCA5 loci. SCA2 patients showed higher occurrence of peripheral neuropathy and slow saccades, rarer corticospinal signs and a milder course of the disease in comparison with SCA1 patients.

Heterogeneous findings in four cases of cerebellar ataxia associated with hypogonadism (Holmes' type ataxia)

We report four sporadic cases of cerebellar ataxia associated with hypogonadism. All patients were female. The neurological symptoms appeared in the first three decades. Apart from ataxia, the most frequent features were nystagmus, dysarthria, mental impairment, brisk tendon reflexes, skeletal deformities, peripheral neuropathy, and tremor. Neuroimaging studies showed constant cerebellar atrophy, in some instances associated with involvement of either grey or white cerebral matter. Neurophysiological studies demonstrated an axonal neuropathy. Endocrine evaluation showed heterogeneity of the hypogonadism, which was hypogonadotrophic in one patient and hypergonadotrophic in the other three. One patient had partial deficiency of muscle cytochrome c oxidase. The syndrome appears to be a heterogeneous multisystem disorder and in some cases a mitochondrial metabolism deficiency could be suspected.

Influence of age, gender, height and education on vibration sense. A study by tuning fork in 192 normal subjects.

We measured perception time of the vibratory stimulus from a 128 cps tuning fork in 96 male and 96 female normal subjects equally subdivided into 8 age decades. The following sites were examined: clavicula, olecranon, styloid apophysis of ulna and radius, anterosuperior spina of ilium, rotula (patella), internal and external malleolus. Reproducibility between different examiners and between tests by the same examiner on different days was good. There was a marked regional variation with longer perception times at the distal regions of upper limbs. A non linear age-related decrease in vibration sense was found in all regions. Males had longer perception times at clavicula, females at distal limbs; the latter finding might be explained by shorter stature in females. Perception times at distal limbs were longer in subjects with higher education levels. The study provides normative data for vibration sense in different regions and defines the effects on it of age, gender, height and education.

Smell and taste acuity in epileptic syndromes.

Taste and smell acuity were determined in 50 normal subjects and 48 epileptic patients by means of Henkins method. Smell detection thresholds are greatly reduced in epileptic patients, mainly those suffering from partial seizures with complex symptomatology. Epileptic patients show also a reduced threshold for sweet and bitter taste. Age, sex and antiepileptic drugs do not affect taste and smell acuity. The significance of these findings in the pathogenesis of epileptic seizures is discussed.