Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications.

Intravenous administration of methylphenidate hydrochloride, a central stimulant, was unexpectedly found to exert a potent analgesic effect on primary sensory symptoms in a group of patients with Parkinson's disease. This effect, which has now been studied in a short-term, double-blind, placebo-controlled experiment, subsequently disappeared if patients were pretreated with a beta-blocker or with a serotonin antagonist. Cerebrospinal fluid monoamine metabolites were determined in some of these patients, and the 5-hydroxyindoleacetic acid level was found to be significantly lower than in parkinsonian patients without pain and in normal volunteers. Given the mechanism of action of methylphenidate on the central nervous system, the adrenergic and serotoninergic mediation of its analgesic effect, and the demonstration of impaired central serotonin metabolism in the patient group, it is concluded that not only central dopaminergic deficiency but also altered noradrenergic and serotoninergic transmission in the spinal cord are quite likely to play a role in the pathophysiology of pain in Parkinson's disease.

High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations.

We conducted a double-blind trial of high-dose parenteral 6-methylprednisolone (MP) and placebo on 23 patients with acute MS. After the double-blind trial, the patients were given corticosteroids in gradually decreasing doses. The frequency of improvement was significantly higher and the bout duration significantly lower in the MP group than in the placebo group. The first signs of improvement (3 to 6 days after starting MP) were associated with a marked decrease in the rate of CNS IgG synthesis, but IgG CSF oligoclonal bands did not change. CNS IgG production slowly returned toward baseline despite progressive clinical improvement.

A syndrome resembling limbic encephalitis, associated with bronchial carcinoma, but without neuropathological abnormality: a case report.

A patient, suffering from an oat-cell bronchial carcinoma, presented with complex partial seizures, complete loss of recent memory, mild disorientation and confabulation. There was no complaint of anxiety. The rest of the neurological examination and four computed tomographic scans of the head were normal. Repeated EEG recordings were abnormal. Antiepileptic and antipsychotic treatment led to full remission within 10 days. Post-mortem examination of the brain revealed no pathological changes.

The effects of the increase of arterial potassium upon the excitability of normal and dystrophic myotonic muscles in man.

Progressively increasing concentrations of potassium chloride were administered intra-arterially to patients affected with dystrophia myotonica (Steinert's disease) and to healthy volunteers before and after parenteral taurine treatment. Changes in the excitability of thenar eminence muscles were related to plasma potassium concentrations. A rise in the plasma potassium brought about a parallel increase of muscular excitability in normal individuals whilst in dystrophic myotonic patients it was associated with a two-phase phenomenon: the severity of myotonia first decreased and then, at higher plasma potassium levels, greatly worsened with the occurrence of spontaneous myotonic discharges. The administration of taurine, a membrane-stabilizing drug, considerably lowered the excitability of both normal and dystrophic myotonic muscles. The effects of potassium and taurine on muscular membrane conductance may explain the observed changes in muscular excitability.

The quantification of myotonia. A problem in the evaluation of new antimyotonic drugs.

The evaluation of an antimyotonic drug is often difficult since the severity of myotonia is itself hard to assess. The rise in arterial potassium level produced by the infusion of increasing concentrations of potassium chloride brought about reproducible changes in the excitability level of myotonic muscles proportional to the plasma potassium concentration. The excitability changes were assessed by three methods commonly used for evaluating antimyotonic drugs. The duration of the electromyographic relaxation time after maximal voluntary effort proved to be the only test which reliably assessed the variations of muscular excitability proportional to the increased plasma potassium. By contrast, the duration of percussion- or electrically-induced myotonic after-discharges was extremely variable and independent of plasma potassium.

Apomorphine SC treatment in parkinsonian patients with long-term L-dopa syndrome during L-dopa drug holiday.

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.

Isolated hypophyseal tuberculoma: case report.

A 45-year-old woman, lifelong resident in Turin presented an isolated tuberculous granuloma of the hypophysis with no other systemic localizations. Diagnosis could be established only by biopsy. With antituberculous therapy the intracellular tumor regressed but not the endocrine disorders.

[Neurotoxic action of muzolimine at high doses in uremic patients. Observation of a group of 29 subjects]. / Azione neurotossica della muzolimina ad alte dosi in pazienti uremici. Osservazione su un gruppo di 29 soggetti.

We report the results of a study on 29 patients affected by renal chronic insufficiency and treated with high doses of muzolimine. From our data it results that to the muzolimine is probable due a neurological syndrome very similar to combined sclerosis. Up today, it is not possible to know how and where the muzolimine develops its neurotoxic effect.

[Hypokalemic myopathy caused by fluoroprednisolone in a nasal spray. Observations 2 cases]. / Miopatia ipokaliemica da fluoroprednisolone in spray nasale. Osservazioni su due casi.

Reference is made to the picture observed in two patients with flaccid tetraparesis, severe hypopotassaemia, and myoglobinuric muscle necrosis (hypokalaemic myopathy). Recent onset of hypertension was a feature of both cases. Initially, however, no reason could be assigned for this, nor for the massive loss of potassium. Numerous investigations in the first case (and relatively quick verification in the second) incriminated a steroid, 9-alpha-fluoroprednisolone acetate, in a nasal spray. This has often been reported as the cause of an iatrogenic syndrome due to excess of mineral corticoids, with hypertension, hypokalaemia and alkalosis, suppression of plasma renin activity, and reduction of blood and urinary aldosterone, all of which were observed in these two patients. Withdrawal of the drug and treatment with potassium chloride led to relatively rapid normalisation of the serum electrolytes. Recovery of muscle strength took place after about 20 days, almost at the same time as the normalisation of muscle enzymes. Hypertension, on the other hand, regressed slowly. The nexus between chronic use of the spray and the occurrence of hypokalaemic muscle necrosis is examined in detail. Stress is laid on the importance of specific investigation of the prior use of intranasal steroids in the differentiation of muscle disturbances due to potassium depletion.

[Preliminary open multicenter study on the anti-tremorigenic effectiveness of bornaprine (Sormodren)]. / Studio preliminare multicentrico "in aperto" sulla efficacia antitremorigena del bornaprine (Sormodren).

Out of 1500 patients suffering from tremor of diverse origin, reliable data on 521 were selected for analysis. The drug was given for over two months (mean daily dose 8 mg) and effectively reduced all kinds of tremor by an average 50%. The only side-effects occurring with any frequency were dryness of the mouth and constipation. The data collected show bornaprine to have a beneficial effect on all types of tremor.

[Aspects of phosphorus and carbohydrate metabolism in amyotrophic lateral sclerosis]. / Aspetti del metabolismo fosfo-glicidico nella sclerosi laterale amiotrofica

The behaviour of glycaemia, insulinaemia, phosphoraemia, somatotropinaemia,free glycerol and triglyceridaemia was studied in six patients with A.L.S. following sugar load (1 g/Kg) in fasting. The results of glycaemia and insulinaemia were in tune with published data which have pointed to reduced sugar tolerance and reduced insulin secretion in patients with A.L.S. In the present experiments, particularly significant were the phosphoraemia responses. The failure of inorganic phosphorus values to fall after glucose loading suggests that the glycidic intolerance of these patients is related above all to a reduction in functioning muscular mass rather than to insufficient insulin secretion. The reduction in nervous tissue may also be of importance in this sense. In fact, not all biohumoral parameters investigated were similar to those of diabetes because the behaviour of somatotropinaemia, free glycerol and plasma triglycerides was normal. The changed behaviour of phosphorus would thus indicate altered glucose uptake at peripheral tissue level.

[Neuropsychiatric findings in a case of paramyoclonus multiplex]. / Indagine neuro-psichiatrica su di un caso di paramioclono multiplo

In a subject affected with multiple paramyoclonus, showing asyncronous, bilateral, intermittent, spontaneous myoclonic jerks, a neuro-psychiatric investigation was performed. Several day-time poligraphic recordings were normal, while the night-time ones showed the lack of myoclonic jerks throughout the sleep. Metrazol activation pointed out a probable hyperexcitability of brain stem reticular formation. The psychiatric investigation, performed with a psychodynamic approach let realize the existence of a distortion of neuro-psychological functions due to an impaired elaboration of emotional information and psycho-structuring engrams. The Authors conclude for a posible convergence of biological and psychological factors causing the clinical symptoms.

[Preventive anti-epileptic action of taurine administered by direct cortical perfusion]. / Azione antiepilettica preventiva della taurina applicata mediante perfusione corticale diretta

To test taurine preventive antiepileptic effect a 90-minute taurine cortical perfusion was made to 8 cats in the left sensory-motor area. A cobalt lesion was then made in the same area following routine. In all cats the beginning and subsequent development of the interictal and ictal epileptic picture were remarkably delayed in comparison with a control group of animals without taurine pretreatment. The taurine preventive action, as the consequence of its brain uptake, is discussed in comparison with the lack of taurine preventive action, when administered intraperitoneally (MUTANI et al., in press). The possibility of the taurine uptake by the normal brain and, therefore, of the prevention of the epilepsy would be related to the different anatomo-physiologic features of the barriers met in the two routes of administration.

Levels of free amino acids in serum and cerebrospinal fluid after administration of taurine to epileptic and normal subjects.

The modifications associated with taurine treatment of the free amino acid content of serum and cerebrospinal fluid were investigated in epileptic and control subjects. In patients with epilepsy the main findings were, in the serum, the correction toward normal of the amino acid levels that were low prior to therapy, and in the cerebrospinal fluid, the increase up to above-normal levels of glutamic acid, greatly diminished before treatment. Thus taurine, which has an anticonvulsant action appears to partially correct the amino acid imbalance in epileptics. The monitoring of taurine-induced glutamate changes in the cerebrospinal fluid could help to establish the correct therapeutic dose.

[Bisynchronous discharge of symmetrical cortical epileptogenic foci and thaurine resistence (author's transl)]. / Resistenza alla taurina della bisincronia di scarica di foci epilettogeni corticali simmetrici

The possible preventive action of taurine administered through a cortical perfusion, has been studied in bilateral and simmetrical foci with bisynchronous discharge. The data obtained showed that: 1)taurine preventive action is less remarkable in bilateral and simmetrical foci; 2) when administered trough the appropriate route, taurine always has a preventive antiepileptic effect. Our data, compared to those of Marcus e al., confirme that bisynchronous discharge, resistant to taurine preventive and terapeutic action, is the obligatory expression of interactions of bilateral and simmetrical foci.

Free amino acids in serum of patients with epilepsy: significant increase in taurine.

More than half the amino acids determined in serum were lower in patients with epilepsy than in control subjects. Taurine was the only amino acid to be increased in epilepsy. The changes could represent a compensatory metabolic reaction to limit the imbalance of amino acids in epileptic brain and to facilitate uptake of taurine, which has an anticonvulsant action.