Debora Soragna

Cognitive impairment and cerebral atrophy in “heavy drinkers”

1. Aim of the work was to verify the following three hypotheses in alcoholics: a) right hemisphere; b) diffuse brain deficit; c) anterior brain deficit, by means of a neuropsychological and a neuroradiological assessment. 2. 15 alcoholic right-hand male subjects and 15 matched controls were enrolled in the study. 3. Specifically designed neuropsychological testing was performed to investigate logical abilities, selective attention and memory. 4. Neurological investigation was performed by a standard CT scan to assess the degree and localization of brain damage. 5. Alcoholics performed worse than controls on some neuropsychological tests, i.e. Attention Matrices Test, Verbal Judgement Test, Forward Digit Span, Story Recall and Remote Memory Test. The analysis of variance adjusted by the attentional score showed no significant differences between alcoholics and controls. 6. Neuroradiological data showed a preeminent and a more frequent atrophy of the frontal region. 7. No correlations emerged between neuropsychological and neuroradiological data. 8. In conclusion, the hypothesis of anterior brain deficit seems to be confirmed by our study.

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit

1. The differential role played by blockade of D-1 or D-2 dopamine receptors in mechanisms underlying seizures was studied in a model of EEG after-discharge induced by electrical stimulation of selective brain regions (dorsal hippocampus and amygdala) in the rabbit. 2. The D-2 antagonist haloperidol (1 mg/Kg) increased significantly after-discharge duration after stimulation of either hippocampus or amygdala and lowered after-discharge threshold in few animals. 3. The D-1 antagonist SCH 23390 (0.3 mg/Kg) caused no changes following stimulation of amygdala and reduced after-discharge duration when hippocampus was stimulated. 4. Haloperidol exerted a proconvulsant action in this experimental model, having a clearer influence on D-2 receptors. SCH 23390 had no effect on amygdala whereas it exerted protection on the hippocampus. 5. The present data suggest that D-1 and D-2 receptors have different roles in generating and spreading the epileptic activity.

Dopaminergic pathways involvement in Kennedy's disease: neurophysiological and [123I]β-CIT SPECT findings

Sirs: Kennedy’s disease (KD) is an X-linked recessive late-onset lower motor neuron disease caused by an expansion of the trinucleotide repeat (CAG)n in the first exon of the androgen receptor gene [1]. It is characterized by slowly progressive limb and bulbar muscle weakness and signs of androgen insensitivity [2]. Isolated cases associated with clinical signs of central nervous system damage have been reported [3, 4] and in one case the neuropathological study provided the evidence of cerebral structures involvement [4]. We report a man who presented with prominent distal muscular atrophy, early and severe ponto-bulbar impairment associated with extrapyramidal features. The patient, first complained of an irregular tremor of both hands, dysarthria and dysphagia at the age of 56 years. Ponto-bulbar impairment rapidly worsened till the patient developed an aspiration pneumonia and enteral feeding had to be started. At the age of 62, general examination was within normal limits, in particular neither gynaecomastia nor signs of hypogonadism were present. Neurological examination showed severe facial diplegia, marked wasting of the tongue, dysarthric speech, distal amyotrophy, absence of deep tendon reflexes and diffuse fasciculations. In the upper limbs, an irregular tremor of great amplitude was present during rest and activity. There were no sensory abnormalities, or signs of cerebellar, pyramidal, autonomic, or cognitive involvement. At first the patient was treated with beta-blockers and trazodone, without any benefit. During a four year follow-up we observed a very slow progression of distal amyotrophy and, the development of bradykinesia, axial rigidity and stooped posture. Levodopa/benserazide (100/25 mg) was administered at the dosage of 250 mg per 3/die with a poor improvement on the extrapyramidal features. Two years later the patient died of an acute myocardial infarct. The relatives refused the consent for autopsy. Neurophysiological and histological findings in a sural nerve biopsy specimen revealed a diffuse and severe axonopathy. The molecular diagnosis of KD was confirmed in the patient, in a sister, and in his nephew (Fig. 1). Electromyographic study of the tremor showed an irregular activity: sometimes synchronous, sometimes alternating, with irregular frequency (range 4–8 Hz) and amplitude. Brain MRI scan was within normal limits. A SPECT study using [123I]βCIT detected a normal uptake of the tracer in the caudate nuclei and a marked and symmetrical reduction in the putamen, resembling the typical pattern of a presynaptic dopaminergic extrapyramidal disease (Fig. 2). In our patient clinical, neurophysiological and neurofunctional findings showed the coexistence of KD and an extrapyramidal syndrome which developed with an uncomplete phenotype and an atypical pattern. The presence of a severe and early ponto-bulbar impairment and the prevalence of a distal spinal involvement are rare LETTER TO THE EDITORS

Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits

1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been studied in the rabbit. Subsequently we tested the neurophysiological and behavioural interactions between ondansetron and L-5-HTP induced serotonergic syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.) increase in the cortical power density spectrum, particularly in the range of the lowest frequencies bands. This effect is expression of cortical synchronization. 3. The lowest and mild dose, but not the highest, failed to produce behavioural sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5-HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural pattern characterized by a decrease of cortical power spectrum density and stereotyped movements. The EEGraphic effects were significantly suppressed by administration of mild and higher doses of ondansetron, while the behavioural effects were inhibited by all doses tested. 5. It is concluded that ondansetron acts with considerably efficacy on central nervous system. The administration of low and mild doses shows a singular dissociation between EEGraphic and behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by ondansetron suggests that this drug acts on behaviour only when there is an altered physiological pattern.