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The aims of this study were to assess autonomic nervous function in subjects with recently diagnosed Parkinson's disease (de novo patients) and to evaluate its changes following acute levodopa administration. In 13 patients (8 males, 5 females) and 13 age-matched control subjects, three cardiovascular autonomic function tests (Deep Breathing, Valsalva, Lying to Standing) were performed, the QT interval was calculated on a 12-lead electrocardiogram, and the response of plasma norepinephrine to standing was assessed in basal conditions. The cardiovascular tests and the measurement of the QT interval were repeated in de novo Parkinsonian patients 90 minutes after the administration of levodopa 200 mg per os. The results of the Deep Breathing and Valsalva tests were worse and the QT interval longer in patients than in control subjects (although the differences were not statistically significant). The heart rate increase at 30 seconds after standing up was significantly higher in Parkinsonian patients than in the control group. The response of plasma norepinephrine to standing was similar in both groups. Levodopa administration produced a slight improvement in the Deep Breathing test, a shortening of the QT interval and increased tachycardia on standing. Our data suggest that a mild subclinical impairment of parasympathetic function can be a feature of de novo Parkinsonian patients and that levodopa therapy could have a beneficial effect on this autonomic dysfunction.

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The Long-Term Dopa Syndrome (LTDS) is one of the main problems in the management of advanced parkinsonian patients. A transient L-Dopa withdrawal (Drug Holiday, DH) can be useful to improve the drug response after DH, even if this approach presents risks due to patient akinesia. We tried to verify if Apomorphine sc administration during DH (DH with Apomorphine, DHA) can: a) reduce the risks connected with DH: b) maintain the benefits of DH: c) standardize the duration of DH. Twenty-five parkinsonian patients with LTDS were treated with Apomorphine sc during DH (14 days). No patient had any severe side effects. The follow-up at 180 days, conducted using the Unified Parkinson's Disease Rating Scale, demonstrated a significant improvement in the clinical conditions of about 70% of the patients, allowing a 27.1% reduction in daily L-dopa dosage. DHA can represent a valid therapeutical approach for parkinsonian patients with LTDS.

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Alzheimer's disease (AD) is a central nervous system disorder characterized by the presence of neurofibrillary tangles, neuritic plaques and dystrophic neurones in susceptible areas of the brain. Few options for treatment of AD symptomatology are available. We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel trial consisting of a 90 day treatment period followed by a 30 day single blind placebo administration and by an optional long term period of treatment up to a year with idebenone in open fashion. Ninety two patients entered the study and nine of them dropped out before the first control. Treatment with idebenone was found effective on memory, attention, and orientation and in slowing down the natural progressive worsening of the disease. The most common side effects associated with this treatment were insomnia, gastralgia, nausea, and anxiety. However, all adverse effects were of mild intensity and did not require specific therapies.

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Much evidence suggests that parkinsonian rigidity is due to hyperactivity of a reflex arc. While tendon jerk and H reflex are not modified in Parkinson's disease (PD), the long-latency component of stretch reflex (LLR) shows an increased size in PD. It has been proposed that this modification could account for rigidity. We studied in 14 PD patients and 8 normal subjects the stretch reflex of the quadriceps femoris. The muscle was stretched by a torque motor in two experimental sets: at rest and with voluntary background activity. Latency, duration and size of the reflex were compared in two groups; correlation between size of the reflex and rigidity was investigated. A lower threshold for the reflex was found in PD patients in trials at rest, and LLR showed increased size and duration in trials with background activity. No clear relationships between these data and rigidity were demonstrated.

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A double-blind, placebo-controlled, randomized study is described of an assessment of the efficacy and relative safety of the ergot alkaloid, dihydroergocryptine, on 52 patients with mild organic brain syndrome over a period of three months using a series of neurophysiological tests. The results indicated that short-term treatment with the alkaloid improved memory impairment. The side-effects were mild and transient in both the dihydroergocryptine and placebo groups and there were no alterations in blood chemistry.

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Forty elderly patients (13 men and 27 women, aged 56 to 80 years) were enrolled in a single-blind, randomized, parallel study to assess the efficacy and safety of selegiline (10 mg, once daily) and that of L-acetylcarnitine (500 mg, twice daily) in the treatment of patients with mild-to-moderate Alzheimer-type disorders. The treatments lasted 90 days, after a run-in period of 15 days. An extensive psychometric examination, carried out at baseline and subsequently at every 30 days of treatment, was used for evaluation of efficacy. Drug safety was assessed by noting any adverse effects that occurred during treatment and by performing laboratory tests at the beginning and end of treatment. According to the resulting data, selegiline therapy led to a global improvement in the capacity for the processing, storage, and retrieval of given information. Improvements in verbal fluency and visuospatial abilities were also noted. The marked between-group differences demonstrate that, at the dosage used, selegiline was far more effective than L-acetylcarnitine with respect to the degree of improvement. Finally, tolerability of both drugs was excellent, inasmuch as neither the monitoring for adverse drug reactions nor laboratory tests revealed any abnormalities resulting from therapy.

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Thirty-nine de novo patients with Parkinson's disease were treated with bromocriptine alone and followed on average for 5.9 years. Fifteen of the 39 patients did not complete the first year of observation, 12 of them because of drug intolerance. The symptomatology was tolerated well by other 24 for the first 2 years treatment. During the third year of follow-up levodopa treatment had to be instituted because of loss of response to bromocriptine. The number of fluctuations in disability was smaller in the patients whose symptomatology was controlled by bromocriptine monotherapy than in those requiring levodopa, either alone or combined with bromocriptine.

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Elderly hypertensive patients with psycho-organic syndrome were treated with nicardipine (40-60 mg daily) alone or combined with hydrochlorothiazide (30 mg). This treatment led not only to a significant reduction in blood pressure but also to improvement in the score of the scales used for psychogeriatric evaluation (SCAG = Sandoz Geriatric Assessment Scale and HAM-D = Hamilton Rating Scale for Depression). These findings appear to confirm the possibility to consider nicardipine a drug of first choice for the treatment of arterial hypertension in the elderly with psycho-organic syndrome.

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The study covers 30 patients with idiopathic Parkinson disease, 13 men and 17 women, aged between 50 and 70, on stabilized L-Dopa and/or bromocriptine, which failed to ensure adequate control of the symptoms, especially tremor. To this regimen was added Bornaprine/placebo in randomized sequence. The patients were tested according to the Webster Rating Scale before, during and after each stage of the treatment. Statistical analysis of the results showed the superiority of Bornaprine over the placebo in reducing tremor (p less than 0.01) and, to a lesser degree, some other parkinsonian symptoms. No noteworthy side effects were found apart from dryness of the mouth, which was more frequent with Bornaprine.

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The antidepressant activity of amineptine was evaluated in 34 patients in a double-blind study vs clomipramine. Clinical results, assessed using the Hamilton rating scale for depression, failed to show any significant difference in the activity of the two drugs. Amineptine was however much better tolerated than clomipramine. The antidepressant activity of amineptine was further investigated in an open multicenter study carried out in 351 depressed patients. The significant reductions in the scores of the Hamilton rating scale for depression and the final clinical evaluations (87% favorable results, 69% of which excellent or good) confirmed the therapeutic efficacy of amineptine. Tolerance was excellent also in elderly, at risk patients.

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20 depressed and 20 non depressed patients with Parkinson disease were rated for disability on the Northwestern University Disability Scale and for severity of the "typical" motor symptoms on the Columbia University Rating Scale and were assessed for mental deterioration. The severity of the "typical" symptoms was practically equivalent in the two groups but the depressed patients not only presented mild mental deterioration but were significantly more disabled (less independent) than the patients without depression. A significant correlation was found between severity of depression and degree of disability but not between severity of depression and severity of "typical" motor symptoms. Depression was diagnosed much later than the "typical" symptoms. Only 25% of the depressed parkinsonians had received tricyclic antidepressants, about 20% had been treated with dopamine-antagonist psychotropic drugs and some 50% had received no treatment at all against depression. Timely diagnosis and appropriate treatment of depression in parkinsonian patients limits the effects of a major disabling factor.

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After a definition of the condition and a discussion of its physiopathological significance, the need to examine the patient as a whole and provide total therapy is emphasised with reference to both the literature and personal cases. It is concluded: 1) that the mesodiencephalic structures, especially the hypothalamus, are of primary importance in human physiological and pathological processes. The hypothalamus is the real brain of the viscera, the functional bridge between the hypophysis, the limbic structures and the upper cortical centres; 2) that doctors should consider the role of the hypothalamus in the diagnosis and therapy of the total person: a) in evaluating the patient's real emotional and psychological situation; b) in realising that the simple administration of a drug to cure the organic symptom really means only partial treatment of the patient himself.

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