The association of motor neuron disease (MND) with rapidly progressive aphasic dementia has been recognized as a distinct clinical syndrome within the group of frontotemporal dementias (FTDs). Although the clinical and neuropsychological features of this syndrome have been defined, a small number of post-mortem studies have been published with heterogeneous neuropathological findings. We performed cognitive, neuro-imaging and neuropathological studies on a 71-year-old male with rapidly progressive aphasic dementia and MND. We initially found a selective non-fluent aphasia associated with hypoperfusion of the left frontotemporal cortex. Proton magnetic resonance spectroscopy revealed an asymmetric change of brain metabolites, with greater changes in the left temporal lobe. The bulbar manifestations of MND occurred over the following 6 months, and the patient died of bronchopneumonia. The neuropathological examination revealed loss of neurons in the hypoglossal nucleus and anterior horns of the cervical spinal cord with microvacuolation and dot-like ubiquitin-positive deposits in the frontoparietotemporal cortex, but no changes suggestive of Alzheimer’s, Pick’s or Lewy body disease. These findings support the conclusion that MND with rapidly progressive aphasic dementia is a distinctive clinical entity within the group of FTD-MND.

Design: Prospective 2-year survey from 1 February 1997 to 31 January 1999. Objectives: To compare the route from injury to rehabilitation, and the outcome of care in a large sample of traumatic (T) and nontraumatic (NT) spinal cord lesion (SCL) patients at their ‘first admission’. Setting: T and NT SCI patients consecutively admitted to 37 SCL centres in Italy. Method: Data were recorded on simple, computerised, closed-question forms, which were Centrally collected and analysed. Descriptive and inferential analysis was conducted to define the characteristics and compare the T and NT populations, and to identify correlations among the variables examined: time from the event to admission (TEA); pressure sores (PS) on admission; length of stay (LoS) and destination on discharge. Results: A total of 1014 SCL patients, 67.5% with a lesion of T and 32.5% of NT aetiology were analysed. The subjects in the T group were younger (median 34 versus 58 years), with higher probability of cervical involvement (OR 2.47, CI 1.8–3.4) and completeness of the lesion (OR 3.0, CI 2.3–4.0), shorter median TEA(37 versus 64 days, P<0.0001) and less frequent admission from home (3.6 versus 17.4%) compared to the NT group. TEA and PS on admission were analysed as indicators of the efficacy of the courses from injury to rehabilitation. Longer TEA was reported for people with NT aetiology, admitted to rehabilitation centre (RC), not locally resident, transferred from certain wards and to a lesser degree female subjects and those with complications on admission. PS were associated to completeness of lesion, longer TEA, admission to RC, nonlocal residence and coming from general intensive care units, or general surgery wards. Median LoS was 99 days (mean 116 and range 0–672), and was statistically shorter in the NT group (122 versus 57 median, P<0.00001). Upon discharge, bladder and bowel autonomy were, respectively, obtained in 68.1 and 64.5% of the whole population without significant difference between the T and NT groups. A total of 80.2% of patients were discharged home and the following factors: not living alone, being discharged after longer LoS, having sphincterial autonomy and no PS, were all independent predictors of outcome. Conclusion: There are important obstacles in the admission route to rehabilitation facilities, greater for NT, as longer TEA and more complications on admission testify. Moreover, the LoS is shorter for NT population. Our findings suggest that rehabilitation outcome could be improved through an early multidisciplinary approach and better continuity between acute and rehabilitation care, especially for the ‘neglected’ NT SCL patients.

Background: Superficial siderosis of the central nervous system (SSNS) is caused by cerebral, cerebellar and spinal cord tissue deposition of hemosiderin, often related to repeated episodes of subarachnoid hemorrhage. Typical symptoms include ataxia, sensorineural deafness and dementia. Methods and Results: An elderly patient with SSNS presenting with ataxia, depression and severe visual impairment was admitted to the Unit of Geriatrics of the University Hospital of Perugia, Italy. Late diagnosis and the association of symptoms with SSNS prevented the possible surgical treatment of the disease. Conclusions: Recognition of uncommon clinical variants may facilitate early diagnosis of SSNS and improve therapeutic results.

To the Editor: The very interesting article of Jacobs et al. [8] on Neuropsychological characteristics of dementia in Parkinson's disease (PD) suggests several ideas. A preclinical phase of parkinsonian dementia can be identified, and this preclinical phase presents a specific neuropsychological pattern that can be distinguished from the pattern seen in Alzheimer's disease. Verbal fluency represents the type of cognitive performance that can best be correlated with subsequent development of dementia, and poor performance on these tests would reflect an executive dysfunction due to an involvement of the frontal-subcortical circuits. On the basis of our own results, an early frontal dysfunction can be considered the best predictive factor for the development of dementia in PD. [2] In particular, in an otherwise unselected sample of parkinsonian patients, we found that four different types of relationships can be observed between a frontal syndrome, dementia and PD: (1) no cognitive abnormalities are revealed by neuropsychological evaluation; (2) the frontal symptomatology is associated with a more generalized cognitive impairment; (3) signs of frontal dysfunction constitute the sole cognitive alteration that can be noted; and (4) the neuropsychological examination reveals abnormal cognitive functions that cannot be attributed to a frontal dysfunction. The first pattern can be …

Rats were injected intraperitoneally with varying doses of l-deprenyl (selegiline) followed 2 h later by 30 mg kg−1 2-phenylethylamine (PEA), administered in the same way, and the stereotypic behavioural response elicited was assessed. l-Deprenyl alone at doses of up to 5 mg kg−1 caused no significant behavioural response. Administration of PEA without prior l-deprenyl treatment resulted in only a modest increase in stereotypic behaviour and this was not significantly enhanced by the prior administration 1 mg kg−1 l-deprenyl. When the administered dose of l-deprenyl was increased to 2.5 or 5 mg kg−1, however, the stereotypic behavioural response to PEA was greatly potentiated and in the latter case persisted for 60 min. A dose of 2.5 mg kg−1 l-deprenyl and 1 mg kg−1 rasagiline was shown to result in over 90% inhibition of the monoamine oxidase (MAO)-B from rat liver and striatum, whereas the inhibition of MAO-A was about 60 and 40% in liver and striatum, respectively. The recovery of MAO-B activity in rat striatum and liver following a single i.p. injection of 5 mg kg−1 l-deprenyl gave first-order rate constants of 1.80 and 7.15 h−1, respectively, which corresponded to half-lives of 9.23 and 2.33 days. Similar results were obtained with rasagiline. The corresponding indices of stereotypic response to PEA (30 mg kg−1; i.p.) during recovery from the single dose of l-deprenyl were initially high, but had started to decline by the third day after l-deprenyl treatment and was not significant after day 4. At that time, less than 20% of the striatal monoamine oxidase-B activity had been regained, whereas the recovery of the liver enzyme was about 65%. These data are discussed in terms of the suggested involvement of PEA potentiation in the anti-parkinsonian actions of l-deprenyl and rasagiline and the duration of the ‘wash-out’ period used in studies on the effects of l-deprenyl on patients with Parkinson's disease. The longer duration of the recovery of brain monoamine oxidase B after its selective inhibition and the corresponding behavioural responses of the animals to PEA at same time points, indicate that PEA may have a major pharmacological role in the mechanism of the antiParkinson action of l-deprenyl and rasagiline. Brain monoamine oxidase B inhibition has previously been shown to significantly increases brain PEA and which is capable of releasing dopamine endogeously or that formed from l-dopa.

Parkinsonians with predominantly unilateral signs provide an interesting experimental means to evaluate if asymmetric nigro-striatal degeneration may affect neuropsychological functions. The aim of our study was to establish if the side of onset of idiopathic Parkinson's disease, right (PDR) or left (PDL), determines a selective pattern of cognitive performances. Furthermore, we verified if PDR and PDL groups show a different frequency of dementia. PDR and PDL patients with at least seven years of disease duration, matched for age, schooling, severity of extrapyramidal symptomatology and index of lateralization, were evaluated by using an extensive neuropsychological battery aimed at assessing hemispheric cognitive asymmetries. Current side of greater motor impairment was the same as the one affected at the onset of the disease.Only subtle differences in the profile of neuropsychological dysfunction emerged from the comparison of PDR and PDL subjects. Moreover, the number of parkinsonians showing dementia syndrome was the same in both groups. Our results suggest that the side of onset of motor impairment does not significantly influence the cognitive performances in PD. Subcortical anatomic and/or functional asymmetries seem to play a less important role in the intellectual functions than in motor activities.

In order to evaluate possible progression in the severity of their cognitive impairment, 34 parkinsonians with intellectual impairment were followed longitudinally for 7 years. Each patient was matched for age, sex, severity and duration of illness, and pharmacological treatment, with a parkinsonian patient without cognitive impairment. Results suggest that cognitive deficits are not static but rather there is a progression in the severity. Furthermore, patients suffering from severe dementia are more likely to die during the follow-up period. The prognosis of Parkinson's disease seems to be changed substantially by the occurrence of dementia. The natural history of parkinsonian dementia does not seem to differ from the history of other forms of dementia with a progressively disabling course leading to a complete loss of autonomy.

Finali, Giancarlo, Massimo Piccirilli and Gian Luigi Piccinin: Neuropsychological Correlates of L-Deprenyl Therapy in Idiopathic Parkinsonism. Frog. Neuro-Psychopharmacol. & Biol. Psychiat. 1994, 18(1): 115-128. 1. Monoaminergic neurotransmitter systems are known to play an important role in neuropsychological functions and they are impaired in dementia of DAT and PD. 2. L-deprenyl is a monoamine-enhancing drug which at low doses selectively inhibits MAO-B, an enzyme whose brain activity has been reported to increase in normal aging and neurodegenerative dementing disorders. 3. The authors studied the effects of L-deprenyl, 10 mg/day, on several cognitive domains in idiopathic parkinsonians without dementia. Ten out-patients, treated with levodopa plus DDI, were tested before receiving L-deprenyl and retested six months after they had been treated with the drug. A control group of ten parkinsonian out-patients treated with only levodopa plus DDI, matched for age, educational level, severity and duration of extrapyramidal disease, was tested by the same neuropsychological battery and retested after a comparable time interval. 4. Statistically significant changes were noted in the verbal and visuospatial learning performances of PD patients treated with the combination of L-deprenyl and levodopa.

The brain-derived peptide preparation Cerebrolysin (Cl; EBEWE, Austria) increases the stability of blood-brain barrier (BBB)-GLUT1 transcript. To determine if the increase in BBB-GLUT1 mRNA stability is associated with an augmentation of gene expression, the present investigation studied the effect of Cl on the expression of a BBB-GLUTI-luciferase reporter gene in brain endothelial cultured (ECL) cells. Dose: response studies showed that Cl markedly increased the expression of luciferase when the BBB-GLUT1-reporter gene was used. On the contrary, Cl produced no changes in the expression pattern of the control reporter gene, which lacks the GLUT1 regulatory sequence. Desensitization of the protein kinase C (PKC) receptor with the phorbol ester TPA, or inhibition with either 1-(5-isoquinolinylsuIfonyl)-2-methylpiperazine (H7) or staurosporine, had no effect on the increased levels of luciferase induced by Cl. Transfection efficiency was determined by measuring intracellular levels of the expression vector using a quantitative polymerase chain reaction (PCR) assay. The data presented here demonstrate that Cl increases BBB-GLUT1 gene expression in ECL cells through a mechanism that appears to be independent of activation of PKC.

In a double blind randomized crossover trial lasting 6 months selegiline, a selective MAO-B inhibitor, was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia (DAT). Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment, at the time scheduled for crossover (90 days) and at the end of the trial (180 days). The results suggest that selegiline possesses significant activity on some memory parameters, which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisition.

On the long term Parkinson Disease (PD) treatment is often complicated by the occurrence of motor fluctuations. To find out whether early treatment of PD with levodopa, dopaminoagonists or 1-deprenyl is associated with any difference in motor fluctuations occurrence, the Italian Parkinson Study Groups initiated a multicenter, randomized study. Since November 1988, 475 patients cequiring effective treatment for idiopathic PD have been randomized to receive levodopa, dopoamine agonists or deprenyl. After 2 months of therapy, all patients evaluated with the Unified Parkinson Disease Rating Scale showed a significant amelioration. Daily living activities were more impaired in patients treated with deprenyl. Study design is presented and first resuts are discussed.

Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type (DAT). DAT is not, however, a homogenous phenomenon inasmuch as two forms are distinguishable: early onset (EO) and late onset (LO). Moreover, focal patterns of neuropsychological deterioration fall into various subgroups. According to our hypothesis, DAT patients, who at the onset of the disease mainly manifest memory disorders, also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways. In a 6-month randomized, double-blind, cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients. Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test. The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills. We suggest that L-deprenyl, through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems, positively influences cognitive functions and behaviour founded on memory efficiency.

Two forms of verbal fluency test, phonological (FF) and semantic (FS) sets, have been administered to four groups of demented patients: 11 with Alzheimer-type dementia (DAT), 13 with multi-infarct dementia (MID), 8 with Parkinson-Dementia (P-D) and 11 with adult chronic hydrocephalus (ICA). Patients were matched for age, educational level and neuropsychological impairment pattern. Further, ten neurologically healty subjects were selected as control group. Control subjects result to be different from all other groups in both FF and FS; moreover, FF test results to be more impaired in ICA than in DAT. Furthermore, FF is more impaired than FS in P-D and ICA patients. On the basis of our results, verbal fluency tests might represent an useful instrument to differentiate demented subjects from non-demented ones and within demented groups to characterize the different neuropsychological pattern of the cortical and subcortical type of cognitive deterioration.

The monoaminergic neurotransmission defect seen in dementia of the Alzheimer type (DAT) is linked to a known increased activity of type B cerebral monoamine oxidases (MAO-Bs). The use of drugs that are able to block this abnormal activity could therefore be useful in the treatment of some cognitive deficits that characterize DAT. Twenty patients with a clinical diagnosis of DAT and with a slight-moderate mental deterioration were treated with 10 mg/day of L-deprenyl, a selective MAO-B inhibitor, according to a double-blind crossover design vs. placebo. Initial treatment (drug or placebo) was randomly assigned. The patients' cognitive functions were evaluated at baseline and then after 3 and 6 months of treatment with drug or placebo. The patients crossed over treatment after 3 months, without a washout interval. The results of the study show the higher and statistically significant effects of L-deprenyl on memory and attention that seem to be due to an improved function of the monoaminergic systems involved in the process of neuronal degeneration.

Great interest has been recently raised by the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a meperidine analogue capable of producing an irreversible Parkinson's disease. On the basis of papers published during the last years, we examined the structural features and the specific mechanism of action of this substance at the level of dopaminergic neurons. Furthermore, the clinical features of the experimental Parkinson model, obtained by means of MPTP inoculation in various animals and their similarities to the analogous human disease are described. We can conclude that the MPTP discovery enhances the hypothesis that Parkinson's disease can be also attributed to toxic factors.