The effect of amantadine on arousal and EEG patterns in Creutzfeldt-Jakob disease.

In recent years, Creutzfeldt-Jakob disease (CJD) has been supposed to be of viral origin, and amantadine hydrochloride has been suggested as therapy because of its proved antiviral action. We studied nine patients with CJD (confirmed at autopsy in seven). Four were treated with amantadine hydrochloride, in dosages ranging from 3.5 to 15 mg/kg/day for an average period of 32 days. The clinical evolution of their disease was compared with that in five patients receiving only supportive maintenance therapy. The length of survival from the onset of clinical care did not differ significantly between the two groups. Nevertheless, a transient improvement in wakefulness and mentation was observed in three patients treated with amantadine, and EEG changes were observed in two, consisting above all of a reduction in the slow-wave activity and the periodic discharges (PDs). Amantadine administered intravenously did not induce any short-term changes in the PDs or the cyclic alternating pattern.

Double-blind comparison of primidone and phenobarbital in essential tremor.

In a double-blind cross-over trial, primidone was superior to both placebo and phenobarbital in reducing essential tremor in 13 patients. Phenobarbital, at a dosage yielding serum barbiturate levels greater than those seen with primidone, was not better than placebo. Thus, primidone has an effect in essential tremor independent from that of its metabolite phenobarbital.

Immunological abnormalities in a family with progressive external ophthalmoplegia.

The authors report the muscular and humoral immunological abnormalities found in a family with progressive external ophthalmoplegia (PEO) of the "pure" form. Serum circulating immune complexes as determined by the polyethylen glycol (PEG) test and double radial immunodiffusion (DRID) were positive for IgG in both cases studied and for IgM and Clq for the propositus. In the latter circulating auto-antibodies against smooth muscle were also present. Immunohistochemical studies on striated muscle of the propositus showed positive perivascular IgG and IgM staining and IgG in the sarcolemma basement membrane complex. It is suggested that in this family a genetically inherited abnormal immune response to the muscular blood vessel wall has induced vascular injury and ultimately chronic ischemic muscular damage. This is consistent with the view that PEO is a clinical syndrome, i.e. the expression of various defects affecting primarily or secondarily the energy metabolism of the muscular tissue.

Calcium-entry blockers-induced parkinsonism: possible role of inherited susceptibility.

The risk of developing drug-induced parkinsonism (DIP) has been related to a number of factors but it remains up to now poorly defined. The aim of this survey has been to evaluate retrospectively the possible role of inherited components in 25 patients with parkinsonism induced by chronic exposure to the calcium-entry blockers cinnarizine and flunarizine. The finding of higher occurrence of a positive family history for Parkinson's disease (PD) and/or essential tremor (ET) and of higher frequency of secondary cases with PD and/or ET among close relatives of the patients as compared to age-matched controls, suggests the involvement of genetic susceptibility in developing this drug-induced disorder. DIP could be regarded as a multifactorial disease process resulting from potential neurotoxicity of drugs on a background of inherited predisposition.

A case-control study of occupational and environmental risk factors for Parkinson's disease in the Emilia-Romagna region of Italy.

A questionnaire-based case-control study was carried out on 86 patients with neurologist-confirmed idiopathic Parkinson's disease (PD) and 86 controls similar in sex and age. The control group was recruited in outpatient specialist centers of the same University Hospital (glaucoma, psoriasis vulgaris, essential arterial hypertension and renal diseases). Exposure was defined as occupational or residential contact with a given factor for at least 10 consecutive years prior to the onset of PD. Smoking habits were defined by exclusion of those subjects who never smoked. The following risk factors were identified: cranial trauma (OR: 2.88; 95% CI: 0.98-8.49), well water use (OR: 2.78; 95% CI: 1.46-5.28) and occupational exposure to industrial chemicals (OR: 2.13; 95% CI: 1.16-3.91). Among industrial chemicals, only organic solvents were identified as significant risk factors for PD (O.R. : 2.78, 95% C.I. : 1.23-6.26). Whereas no exposure to neurotoxic metals occurred among controls, making the assessment of the O.R. impossible, exposure pesticides and herbicides was similar in the two groups (O.R. : 1.15; 95% C. : 0.56-2-36). Smoking habits was negatively associated with PD (OR: 0.41; 95% CI: 0.22-0.75), confirming the "protective" role of tobacco smoking suggested by many studies. As a whole, these results support the role of environmental factors in the etiology of PD.

L-deprenyl as an adjunct to low-dose bromocriptine in early Parkinson's disease: a short-term, double-blind, and prospective follow-up study.

The therapeutic efficacy of L-deprenyl (10 mg daily) as an adjunct to low-dose bromocriptine monotherapy (up to 25 mg daily) in patients with early Parkinson's disease (PD) was evaluated in a double-blind placebo-controlled short-term study (11 patients) and subsequently in a long-term prospective open follow-up (21 patients) until L-dopa was required, over a 4-year period. The combined regimen of bromocriptine plus L-deprenyl produced a mildly significant improvement, as shown by the majority of clinical rating scales used after 6 weeks of sustained treatment (as compared to bromocriptine alone and bromocriptine plus placebo). In the prospective long-term study, a stabilization of the clinical status was observed until 12 months of sustained treatment, whereas after that, a gradual worsening of the scores on all motor rating scales occurred. However, at 24 months, fewer than one third of the patients had required L-dopa, a proportion comparatively smaller than that reported in the literature with bromocriptine alone. This finding could be related to the persistence of initial symptomatic effect of L-deprenyl, but a slowing action on the course of the disease process exerted by the monoamine oxidase typeB (MAO-B) inhibitor cannot be ruled out.

Primidone in the long-term treatment of essential tremor: a prospective study with computerized quantitative analysis.

The long-term efficacy of primidone (375-750 mg/day) in essential tremor was evaluated prospectively in 11 patients who had shown a favorable response to 4-week treatment with the drug under placebo-controlled conditions. On accelerometric evaluation, the magnitude of tremor after 3, 6, and 12 months on primidone was still significantly reduced compared with the initial placebo period. After discontinuation of primidone, tremor amplitude reverted to the placebo levels. Some loss of efficacy during long-term administration, however, was suggested by the results of self-assessment, physician's assessment, and performance tests. Three patients discontinued prematurely the drug because the sedative effects outweighed the potential therapeutic benefit. Side effects (especially drowsiness and sedation) were common at 4 weeks and 3 months but tended to subside thereafter. It is concluded that primidone retains at least part of its tremorolytic effect for up to 1 year, although the overall clinical benefit is limited in most patients.

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Transient hemiballismus and subclavian steal syndrome. Case report.

Transient hemiballismus was observed in a 74-year-old man, displaying subclavian steal syndrome. Such a correlation has not been previously reported in the literature. In this case, transient hemiballismus seemed to depend on hemodynamic factors, but other mechanisms possibly explaining early recovery of the hyperkinesias are discussed. In particular, stress is laid upon the role of preexisting pathological changes of the central nervous system (diffuse cerebral atrophy) associated to the "releasing" lesion.

[Polycythemic chorea. Description of a clinical case]. / Corea policitemica. Descrizione di un caso clinico.

The authors report a 69-year-old man affected by polycythaemia rubra vera since the age of sixty, who presented persistent left hemichorea of acute onset, occurring ten months before the exacerbation of the haematologic abnormalities. Previously he had been suffering from a transient episode of chorea concomitant with relapsing of polycythaemia. CT scan of the brain showed diffuse cortico-subcortical atrophy, whereas Doppler velocimetry of carotid arteries demonstrated a rise in cerebral blood flow resistance and a stenosis of the right carotid artery in its first tract. Pathogenetic mechanisms of chorea complicating polycythaemia vera are discussed and a multifactorial origin of the syndrome is suggested.

[Epidemiological study on tremor in the aged]. / Studio epidemiologico sul tremore della terza età.

203 hospitalized old-aged patients were examined for the presence of tremor. This physical sign was found in 58.6% of cases. By far the largest diagnostic category resulted that of essential tremor: 46.7% of all patients investigated and 77.8% of all cases of tremor. The frequency of this type of tremor was found to increase proportionally to age. The conclusion is drawn that also tremor, as well as other neurological signs frequently demonstrable in "normal" old people (for example, the so-called primitive reflexes), should be inscribed in the group of the phenomena due to the ageing process itself.

Palatal "myoclonus" and inferior olive hypertrophy with one-sided cerebellar lesion. Clinico-pathological report of one patient.

A case of palatal myoclonus and inferior olive hypertrophy is reported. Lesions located other than in the medulla were cerebellar infarction, lymphomatous infiltrates and, supratentorially, progressive multifocal leukoencephalopathy. It is suggested that double innervation of the olives from either side dentate nucleus may be why in the case reported here and in several cases in the literature, one-sided supra-olivary lesions can produce bilateral hypertrophy. As with palatal "myoclonus" and olivary hypertrophy, it is proposed that if the characteristic rhythmical movements occur, lesions besides those along the dentate-olivary pathway and the olivary hypertrophy itself have to be present.

REM sleep behaviour disorder in Parkinson's disease: a questionnaire-based study.

The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.

A long-term follow-up study of cinnarizine- and flunarizine-induced parkinsonism.

The natural course of calcium-entry blocker-induced parkinsonism was evaluated in 13 elderly patients previously exposed to cinnarizine or flunarizine or both for a median period of 7 months. Clinical assessments were carried out before drug discontinuation and twice thereafter over a period lasting < or = 7 years. None of the patients showed a full recovery of extrapyramidal signs, indicating that the long-term prognosis of the parkinsonism is less benign than previously reported. Two main patterns of clinical outcome were recognized (i.e., "remittent" and "persistent and not progressive" parkinsonism), whereas the development of a progressive disorder was observed only in one patient. No significant correlation was found between the patterns of outcome and some clinical variables, such as total duration of exposure to cinnarizine and flunarizine, cumulative drug dosages, and age at onset of parkinsonism. There was no significant difference in terms of family history of essential tremor or parkinsonism or both among patients with the two main patterns of clinical course.

Fluctuation of arterial blood pressure during end-of-dose akinesia in Parkinson's disease.

The supine and erect arterial blood pressure and pulse rate were measured in 13 patients with Parkinson's disease, chronically treated with levodopa and peripheral decarboxilase inhibitors presenting with or without On-Off phenomenon (end-of-dose akinesia). In the patients with dose-related response fluctuations the mean systo-diastolic blood pressure, both supine and erect, was found significantly higher during the Off phase as compared to the On phase and to that of the control group (patients with stable clinical response). The mean diurnal "excursion" of systo-diastolic supine and erect blood pressure in patients with On-Off phenomenon was significantly larger than in the control group. Although the clinical implications of such findings remain to be established, the results of this study indicate that arterial blood pressure fluctuations are a definite autonomic component of end-of-dose akinesia.

Spontaneous hemiballism and disappearance of parksinsonism following contralateral lenticular lacunar infarct.

Hemiballism was observed in a 77-year-old woman with Parksinson disease after a contralateral lenticular infarct without apparent involvement of the subthalamic nucleus. Parkinsonian signs ipsilateral to the hemiballism remained abolished despite subsequent nearly complete recovery from the hyperkinesias. It is argued that clinical events were due to a single ischemic lesion of the putamen-pallidum complex.

[Barbexaclone in the treatment of the epilepsies (author's transl)]. / Il barbexaclone nel trattamento delle epilessie.

Chronic administration of barbiturates in the treatment of the epilepsies causes sedation. The association of C.N.S. stimulant agents appears to offer a possible advantage. 19 epileptic outpatients were followed up during an "open" trial of barbexaclone (L-1-cyclohexyl-2-methylaminopropan-phenyl-ethyl-barbiturate) over a period of about one year. The drug was effective in primary and secondarily generalized epilepsies, and to a lesser extent in partial complex seizures. The tolerability was good and a reduction of the side-effects due to previous treatment with phenobarbitone has been noticed. The mean dosage of barbexaclone was lower in patients who improved than in those who remained unchanged.