Showing papers in "Acta Neurologica Scandinavica in 1989"

Oxidants and the central nervous system: some fundamental questions: is oxidant damage relevant to Parkinson's disease, Alzheimer's disease, traumatic injury or stroke?

Abstract: Radicals are species containing one or more unpaired electrons. The oxygen radical superoxide (O2-) and the non-radical oxidant hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2- and H2O2 can result in tissue damage, which often involves generation of highly-reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron ions. A major form of antioxidant defence is the storage and transport of iron ions in forms that will not catalyze formation of reactive radicals. Tissue injury, eg. by ischaemia or trauma, can cause increased iron availability and accelerate free radical reactions. This may be especially important in the brain, since areas of this organ are rich in iron and cerebrospinal fluid cannot bind released iron ions. Oxidant stress upon nervous tissue can produce damage by several interacting mechanisms, including rises in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that iron-dependent free radical reactions are involved in the neurotoxicity of aluminium and in damage to the substantia nigra in Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of iron ions may be more generally-useful protective agents than chain-breaking antioxidants.

Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration?

Abstract: – Razor sharp and high iron deposits are present in the substantia nigra (SN). Although the function of such high iron content is not known, the homeostatis of brain iron is important for normal brain function. The participation of free tissue iron in oxidative stress (OS), resulting in the formation of cytotoxic hydroxyl radical (·OH) from H2O2 (Fenton reaction) and promotion of membrane lipid peroxides by ·OH can no longer be questioned as a biological phenomenon. The highly selective increase of Fe2+ and Fe3+ and lipid peroxidation observed in parkinsonian SN points to OS in such brains. Lipid peroxidation proceeds with either Fe2+ or Fe3+ provided a mechanism exists to facilitate the interconversion of iron between its redox states. Indeed H2O2 derived from MAO B reaction and autooxidation of dopamine to melanin in the SN can drive the iron dependent Fenton reaction. Furthermore, interaction of iron with melanin may be even more important considering that melanin avidly binds Fe3+ and reduce it to Fe2+, resulting in ·OH generation. Thus, without evoking environmental neurotoxins, the excessive accumulation of free iron in the SN and “melanintrap'’could be the trigger for accelerated cell death and Parkinsonism.

Normal pressure hydrocephalus. Predictive value of the cerebrospinal fluid tap-test.

Abstract: Twenty-seven patients with normal pressure hydrocephalus were operated upon by a ventriculo-peritoneal shunt. Selection for shunt surgery was based on typical symptoms (gait disturbancy, mental deterioration and urgency incontinence and characteristic changes at cranial computer tomography and/or radionuclide cisternography. Prior to operation a cerebrospinal fluid tap test (CSF-TT) was performed with measurements of psychometric functions and gait pattern before and after a lumbar puncture of 50 cc CSF. Psychometric tests included identical forms measuring complex perceptual functions, Bingley’s memory test and reaction time measured as speed of manual reaction to visual or sound stimuli. The walking test was done by counting how many steps a patient needed for walking 18 meters. Mean of 3 tests was calculated.

Photosensitivity in epilepsy. Electrophysiological and clinical correlates.

Abstract: Photosensitivity is a rare phenomenon found, often more or less accidentally, in approximately 5% of epileptic patients Its pathophysiology still remains largely unsolved and the clinical significance of photosensitivity is controversial The literature on the subject is impressive, yet predominantly anecdotal In this thesis we describe the results of an extensive and standardized study of 100 consecutive photosensitive patients with special emphasis on the clinical history, the seizure history and the electrophysiological findings These are then compared to identical data of an age and sex matched control group, obtained from the same population of epileptic patients, referred to a special (tertiary care) epilepsy clinic In chapter I, the literature is reviewed and photosensitivity as a special form of "reflex epilepsy" is discussed A distinction is made between normal and abnormal reactions on intermittent photic stimulation (IPS) during electroencephalographic (EEG) registrations and the criteria of true photosensitivity are formulated The relation between the presence of photosensitivity during EEG examination and the occurrence of visually-induced epileptic seizures in daily life is discussed As self-induction of seizures has been associated with photosensitivity, an extensive review, including a special reference list (see appendix A), is given concerning such self-inducing behaviour in photosensitive patients A review of photosensitivity as a genetic marker and model of epilepsy concludes this chapter In chapter II the aims of this study are outlined Some general conceptions about photosensitive epilepsy have become widely accepted in clinical practice without much scientific support, ie, the idea that the finding of photosensitivity is synonym with the diagnosis of primary generalized epilepsy Furthermore, photosensitivity is generally believed to be a genetically determined, benign type of epilepsy in childhood and adolescence but when associated with self-inducing behaviour is interpreted as a sign of mental subnormality Whether or not these conceptions are valid and whether photosensitivity is or is not a special subtype of epilepsy remains unsolved In this study we thus set out to answer the following questions: A Are photosensitive epileptic patients different from non-photosensitive patients with epilepsy, with respect to clinical history and, more specifically, to seizure history and family history for seizures? B Is the degree of photosensitivity, established as photosensitivity range, predictive for the liability to visually-induced seizures in daily life? Are detailed laboratory findings concerning sensitivity to television and black-and-white striped patterns of clinically predictive value, eg can patients, liable to TV epilepsy or pattern-induced seizures, be identified by EEG investigations?

Selective neuronal vulnerability following transient cerebral ischemia in the gerbil: distribution and time course.

Abstract: An important feature of ischemic brain damage is the selective vulnerability of specific neuronal populations. We studied the distribution and time course of neuronal damage following transient cerebral ischemia in the gerbil, using light microscopy and 45Ca autoradiography. Following 5 min of ischemia, selective neuronal damage determined by abnormal 45Ca accumulation was recognized only in the hippocampal CA1 subfield and part of the inferior colliculus. Ischemia for 10 to 15 min caused extensive neuronal injury in the 3rd and 5th layers of neocortex, the striatrum, the septum, the whole hippocampus, the thalamus, the medial geniculate body, the substantia nigra, and the inferior colliculus. Progression of the damage was rapid in the medial geniculate body and the inferior colliculus, moderate in the neocortex, striatum, septum, thalamus, and the substantia nigra, and was delayed in the hippocampal CA1 sector. However, the delayed damage of the hippocampus occurred earlier when the ischemia period was prolonged. Histological observation revealed neuronal loss in the identical sites of the 45Ca accumulation. This study revealed that the distribution and time course of selective neuronal damage by ischemia proceeded with different order of susceptibility and different speed of progression.

Prevalence of every night snoring and obstructive sleep apnoeas among 30-69-year-old men in Bologna, Italy.

Abstract: — An epidemiological survey of the prevalence of snoring and sleep apnoeas was performed on 3479 30-69-year-old men living in Bologna, north-east Italy. First a postal questionnaire was sent. It was returned with appropriate answers by 1170. A 20% random sample of those who did not answer were invited by telephone to return the questionnaire. Among these groups 119 (10%) and 19 (5.6%) respectively answered that they always snored. A random sample of 40 every-night snorers were studied by polysomnography. Based on the frequency of every-night snoring and the results of polysomnography we estimated that the minimal prevalence of sleep apnoea among 30-69-year-old men was 2.7% considering an apnoea + hypopnoea index of 10 or more pathological. According to the Lugaresi classification we had a 2.5% prevalence of heavy snorers’ disease (HSD) Stage 1 or higher. These figures indicate that obstructive sleep apnoea during sleep is a major public health problem.

Pathologic laughter and crying in ALS: a search for their origin.

Abstract: Spells of laughter and crying are well known in patients with amyotrophic lateral sclerosis (ALS). Since ALS occurs mostly in older age groups, this brings up the possibility that aging changes in the brain could play a causative role in the origin of such spells. To rule out or at least reduce the complicating factor of aging, a study was made of the incidence of pathologic laughter and crying in patients whose motor neuron disease had started before the age of 45 years. The data were collected from 73 such individuals, all with confirmed ALS. All told, 36 had experienced episodes of pathologic laughter and/or crying. Of these, 20 had bouts of both laughter and crying. 9 bouts of crying alone and 7 spells of laughter alone. Nearly all with such emotional spells had developed bulbar involvement with the illness. The youngest patient with spells was 31 when his illness began and 35 when he started to have bouts of crying.

Associated disorders in myasthenia gravis: autoimmune diseases and their relation to thymectomy.

Abstract: The prevalence of myasthenia gravis (MG) in the counties of Hordaland and Sogn & Fjordane on January 1, 1984 was 9.6 per 100,000 inhabitants. Other autoimmune diseases were found in 11 out of 48 MG patients. The occurrence of autoimmune thyroiditis (5 patients, 10.4%) and systemic lupus erythematosus (4 patients, 8.3%) in the MG patients was clearly higher than that reported in the general population. Rheumatoid arthritis was found in 2 patients (4.2%). The autoimmune diseases were mainly recorded among the nonthymectomized MG patients. In addition to those with definite diseases of autoimmune nature, 3 other MG patients had thyroid antibodies and 1 had antinuclear factor without clinical evidence of autoimmune disease. Seven MG patients (14.6%) had unspecific arthralgia during active periods of MG. Two MG patients had ankylosing spondylitis.

A clinical patho-anatomical study of clinically silent multiple sclerosis.

Abstract: This is the first study on the frequency, size, number, and location of plaques in clinically silent MS. Among the present 18 patients in whom MS was unexpectedly diagnosed at autopsy, it had been clinically silent in 13. An estimate of the prevalence of silent MS is about 25% of that diagnosed in vivo. In the silent group, the MS plaques were located mainly in the periventricular areas, and this may explain the silent nature of the disease.

The pharmacology of selegiline ((-)deprenyl). New aspects.

Abstract: Male rats were treated from the end of their 2nd year of life either with saline (1 ml/kg, s.c.) (n = 66) or with deprenyl (0.25 mg/kg, s.c.) (n = 66) three times a week until death. Whereas none of the two-year-old saline-treated rats displayed full scale sexual activity, this appeared in 64 out of 66 rats on deprenyl. The longest living rat in the saline-treated group lived 164 weeks. The average lifespan of the group was 147.05 +/- 0.56 weeks. The shortest living animal in the (-)deprenyl-treated group lived 171 weeks and the longest living rat died during the 226th week of its life. The average lifespan was 191.91 +/- 2.31 weeks. This is the first instance that a well-aimed medication prolonged lifespan of members of a species beyond their maximum age of death (182 weeks in the rat). A close relation between sexual activity and lifespan was detected. Male rats (n = 94) selected from an 8-month old population as sexually inactive ones were found to be miserable learners. This group was treated either with saline (1 ml/kg, s.c.) (n = 46) or with (-)deprenyl (0.25 mg/kg, s.c.) (n = 48) three times a week for 36 weeks. Their performance in the shuttle box during 5 consecutive days was tested before and after treatment. The total number of conditioned avoidance responses (CAR) which remained unchanged in the saline-treated group (6.53 +/- 1.41 before and 5.98 +/- 1.15 after treatment) increased from 5.57 +/- 0.65 to 20.73 +/- 1.39 (p less than 0.001) in the (-)deprenyl-treated group of rats. (-)Deprenyl-treatment (0.25-2 mg/kg, s.c., daily for 21 days) increased superoxide dismutase (SOD) activity in the striatum of CFY rats, whereas clorgyline-treatment (0.1-1 mg/kg) inhibited it.

Soccer injuries to the brain. A neurologic and electroencephalographic study of former players.

Abstract: Thirty-seven former football players of the Norwegian national team underwent a neurological and electroencephalographic (EEG) examination to investigate the incidence of head injuries due to heading the ball. Sixteen players complained of protracted and permanent symptoms commonly attributed to the post-concussional syndrome: headache, irritability, dizziness, lack of concentration and impaired memory. A significantly increased incidence of EEG abnormalities was found in players compared with matched controls. The high incidence of EEG changes is probably the result of a cumulative effect due to repeated head traumas.

Pharmacokinetics and metabolism of selegiline

Abstract: Selegiline is readily absorbed from the gastrointestinal tract. It is distributed rapidly into the tissues, including the brain. It is the L-form of selegiline that is an active MAO-B inhibitor, the D-(+)-form being 25 times less active. Selegiline is metabolised into L-(-)-desmethylselegiline (DES), L-(-)-amphetamine (A) and L-(-)-methamphetamine (MA), mainly in the liver. We measured the steady state concentrations of the metabolites in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's or Alzheimer's diseases who were on continuous selegiline therapy. The mean concentrations in serum and CSF were similar, and were not affected by the addition of levodopa. The mean concentrations of patients with Alzheimer's or Parkinson's disease were 6.5 +/- 2.5 ng/ml for A, 14.7 +/- 6.5 ng/ml for MA and 0.9 +/- 0.7 ng/ml for DES. The metabolites of selegiline were excreted in urine, and the recovery as metabolites was 87%. Due to the stereospecificity and the low CSF concentrations of the (-)amphetamine metabolites during the therapy with 10 mg selegiline, these metabolites do not seem to contribute significantly to the clinical efficacy of selegiline.

Zinc, copper and magnesium concentration in serum and CSF of patients with neurological disorders.

Abstract: Zinc (Zn), copper (Cu) and magnesium (Mg) concentrations in cerebrospinal fluid (CSF) and serum were determined with atomic absorption spectrophotometry in 74 patients suffering from various neurological diseases, and in 28 healthy controls. Increased CSF zinc levels were found in the group of peripheral nervous system diseases (P less than 0.01) and in the cases of different neurological syndromes with increased CSF protein concentration (P less than 0.001). Increased CSF and serum copper levels were found in the cases with increased CSF protein levels (P less than 0.05). It is probable that the damaged blood-brain-barrier (BBB) permits the passage of the trace elements Zn, Cu and of Mg into the subarachnoid space. Decreased serum Cu levels (P less than 0.01) were found in the group of multiple sclerosis (MS). The findings are correlated to those of previous communications.

Decreased myelin lipids in Alzheimer's disease and vascular dementia

Abstract: The lipid composition of white matter and myelin from the semioval centre was studied in autopsy material from cases with Alzheimer's disease (AD) (n = 11), vascular dementia (VD) (n = 7), and age-matched controls (n = 11). In AD and VD the white matter content of phospholipids and cholesterol was reduced to 72-76% of the control values (P less than 0.01), the diminution of cerebrosides and sulphatides was more pronounced (55-69%) (P less than 0.001) while the concentration of gangliosides did not change significantly (87-90%). The myelin composition was the same in the 3 groups, suggesting that the white matter involvement is not caused by alteration of the myelin structure. The altered lipid composition in white matter in AD and VD suggests that the myelin sheath is the primary lesion site.

Status epilepticus in the elderly: etiology, seizure type and outcome

Abstract: We have studied status epilepticus among 342 patients who had their first seizures after the age of 60 years. One hundred and two patients (30%) had status epilepticus. Cerebrovascular disease (35%) was the leading cause of status, followed by head trauma (21%), multifactorial etiology (11%), metabolic disorders (10%), brain tumors (8%) and CNS infection (2%). The etiology of status remained undetermined in 13 patients (13%). The majority (80%) had partial status or generalized status with focal onset. Overall mortality was 35%.

Risk factors in multiple sclerosis: a population-based case-control study in Hautes-Pyrénées, France.

Abstract: A population-based study of the prevalence and risk factors of multiple sclerosis (MS) was conducted in the Hautes-Pyrenees, the southwestern region of France. The prevalence rate per 100,000 was equal to 40. Data on the past medical history of 63 MS patients and matched controls were collected. The frequency and age at occurrence of common childhood infections were similar for both the MS cases and controls. There was no difference between the frequency of vaccination for MS patients and for controls. However, the age at which MS patients were immunized against poliomyelitis was significantly higher than the corresponding age for controls (15.8 years versus 8.9 years, P less than 0.01). Antibody titers for various viruses were measured. The mumps antibody titer was significantly higher in the MS patients than in the controls. Also, MS patients tended to have higher titers for measles antibodies.

Neurotransmitter deficits in a non-multi-infarct category of vascular dementia.

Abstract: — Brain tissue from 9 severely demented patients cared for in psychiatric long-term wards and with records of stroke episodes, macroscopic signs of brain infarcts and with no clinical evidence of senile dementia of the Alzheimer type was investigated and compared with control material. The mean volume of the brain infarcts in this vascular dementia group was only 6.8 ml. Pronounced disturbances of the serotoninergic and cholingergic systems were found in subcortical and cortical grey matter. These widespread neurotransmitter changes can hardly be explained by the localized brain infarcts per se, but suggest the existence of another category of vascular dementia. Since the neurotransmitter disturbances were found to be similar to those of Alzheimer's disease and senile dementia of the Alzheimer type, it seems more likely that they indicate a common pathway for dementia disorders than that they serve as markers of different dementia categories.

White matter low attenuation on computed tomography in Alzheimer's disease and vascular dementia--diagnostic and pathogenetic aspects.

Abstract: Demented patients with early-onset Alzheimer's disease (AD) (n = 17), late-onset Alzheimer's disease (n = 30) and vascular dementia (VD) (n = 20) were studied with computed tomography of the brain. Semiquantitative evaluation of white matter low attenuation (WMLA) and central and cortical atrophy was performed without knowledge of the clinical diagnosis. In early onset AD there was almost complete absence of WMLA and central atrophy compared with the other groups, which showed moderate to severe changes. This suggests that early-onset AD should be separated from the late-onset form. The increased systolic blood pressure found in the WMLA group supports the opinion that WMLA has a vascular origin. The high percentage of WMLA in VD and late-onset AD indicates that subcortical factors have to be considered in the pathogenesis of these disorders.

Risk factors in intracranial saccular aneurysms. Aspects on the formation and rupture of aneurysms, and development of cerebral vasospasm.

Abstract: Intracranial saccular aneurysms have been a well-known clinical and pathological entity for over two centuries. The pathophysiological events that lead to aneurysm formation and rupture are, however, poorly understood. Besides an HLA-associated genetic factor, the most widely accepted risk factors are arterial hypertension, female gender, and increasing age. Some aneurysm patients have a deficient formation of Type III collagen. This seems to interfere with the mechanical integrity of the cerebral arterial wall encouraging aneurysm formation. While some of the risk factors may be involved in the process of aneurysm formation, others may be of importance in the actual aneurysm rupture. Medical and surgical developments have only had a slight impact on mortality rates from aneurysm rupture. The principal cause of death and disability is cerebral arterial spasm. Considerable effort has been expended in investigating the etiology of this phenomenon. Previous studies have failed to yield conclusive evidence of the causative agent(s) or the nature of cerebral artery narrowing. The time course of vasospasm after the onset of subarachnoid hemorrhage is consistent with an immune-mediated response, and more recent observations suggest that immunological processes including activation of the complement system may be involved. Missed minor bleeding episodes may thus be a risk factor for aneurysm patients in respect to the development of cerebral vasospasm.

Prognosis in solitary intraventricular haemorrhage. Clinical and computed tomographic observations.

Abstract: Isolated intraventricular haemorrhage (IVH) in the absence of parenchymal haematoma is unusual. Fifteen patients with solitary IVH among 170 with intracranial haemorrhage were studied. Clinical details and computed tomographic features were analysed to evaluate the prognostic significance of various clinical and CT parameters. Outcome is affected by hypertension, level of consciousness, clinical progression, pupillary changes and restriction of eye movements. Factors found on CT to have prognostic significance included degree of ventricular bleed, presence of cisternal bleed, hydrocephalus and cerebral atrophy.

Selective vulnerability of pigmented dopaminergic neurons in Parkinson's disease.

Abstract: From a neuropathological point, the diagnosis of Parkinson's disease is confirmed by a neuronal cell loss and the presence of Lewy bodies in the substantia nigra. In Parkinson's disease, the precise type of nigral neuron which degenerate still remains unknown. Are all types of neuron similarly injured, are only subpopulations of neurons vulnerable? In an attempt to answer the question, a qualitative and quantitative analysis of the distribution of dopaminergic cells, as identified by immunohistochemistry with a specific antibody against tyrosine hydroxylase, was performed in the ventral mesencephalon of control subjects and patients who died with a clinical diagnosis of Parkinson's disease. In control brains, two types of catecholaminergic neurons were evidenced; some contain visible-neuromelanin, others do not. In patients with Parkinson's disease, the tyrosine hydroxylase positive cells which contained the pigment were the most vulnerable.

Nimodipine in acute ischemic stroke: a double-blind controlled study.

Abstract: — Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.

Neurochemical perspectives to the function of monoamine oxidase.

Abstract: Dopamine (DA) is degraded in part by MAO, an intraneuronal and glial enzyme localized at the outer mitochondrial membrane. DA is a good substrate for MAO-B and selegiline enhances DA-transmission and improves akinesia of Parkinson's disease (PD) by selective MAO-B blockade. Immunocytochemistry (ICC) and histochemistry (HC) demonstrate that neurons of substantia nigra (SN) lack MAO near totally (but see Moll et al 1988). Consequently, inhibition of MAO-B in this brain area occurs mainly in glial cells. Therefore an increase of DA in glia seems to be of long-lasting therapeutic benefit in PD. In addition, synthesis of hydrogen peroxide generated via MAO-B is blocked by selegiline. By this toxicity by endogenous free radicals is diminished. Furthermore, exogenous neurotoxicity by MAO-B substrates can be prevented by inhibition of MAO-B, while such MAO-A substrates are metabolized at the level of the MAO-A containing endothelium of capillaries. As conclusion, selegiline is a safe inhibitor of MAO-B that reduces neurotoxicity possibly triggering PD. (Table: see text).

Neurobehavioral findings in whiplash patients with long-lasting symptoms.

Abstract: Thirty-four patients with persistent symptoms following whiplash injury and 21 controls with somatic complaints resembling those of the whiplash patients, but with no history of trauma, were studied. Forty-eight neuropsychological test variables were analyzed. The results indicated that whiplash patients with chronic symptoms are not much impaired in their performance as compared with controls. The differences found were not sufficiently strong to be taken as consistent evidence of brain damage occurring as a sequela of whiplash injury.

MPTP-induced parkinsonism as a model for Parkinson's disease.

Abstract: – It is now well recognized that 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) can induce a syndrome in human and non-human primates similar to Parkinson's disease. This highly selective neurotoxin, which affects specific catecholaminergic nuclei in the brainstem, has provided an important new tool for the study of Parkinson's disease. In this article we review several specific areas related to current research on MPTP, including the question of disease progression, issues regarding the validity of the animal model induced by MPTP, the role of aging in regard to its neurotoxicity and Parkinson's disease, and new therapeutic strategies that have evolved from basic research with the compound. We conclude that both clinical and basic research stemming from the discovery of MPTP have provided valuable insights regarding both the cause and treatment of Parkinson's disease.

Selegiline in the treatment of Parkinson's disease.

Abstract: Selegiline is a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B). It also inhibits the reuptake of catecholamines into the presynaptic nerve and enhances the synthesis of dopamine by blocking the presynaptic dopamine autoreceptors. Thanks to these properties it potentiates and prolongs the duration of action of levodopa. Several clinical trials have shown its efficacy as an adjuvant to levodopa therapy. Improvement in parkinsonian disability and reduction of fluctuations in disability can be achieved by adding selegiline to the prevailing levodopa therapy. End-of-dose type fluctuations, in particular, react favourably to selegiline. Side-effects of the therapy can be managed by reducing the dose of levodopa. According to preliminary studies selegiline may also have some benefit as monotherapy in de novo parkinsonian patients. High doses of selegiline have been found to have some antidepressant efficacy, especially in patients with nonendogenous depression. It may also have an effect on bradyphrenia and some symptoms of cognitive dysfunction and dementia. In animal models selegiline has been shown to prevent parkinsonism caused by MPTP and also to increase the life span of rats. Whether selegiline slows down the progression of Parkinson's disease needs further examination.

The effect of hemiplegia on bone mass and soft tissue body composition.

Abstract: The content of bone mineral (BMC), lean tissue, and fat tissue were measured by single and dual photon absorptiometry in both the paretic and the non-paretic limbs of 15 patients, hemiplegic due to cerebrovascular accident 23-38 weeks earlier. Compared with the non-paretic arm, the paretic arm had approximately 10% lower (P less than 0.01) BMC. This difference was largest at the measuring site with the highest ratio of trabecular to compact bone. The paretic leg had a 4% (P less than 0.001) lower BMC than the non-paretic leg. For both the arms and the legs, the lean content was lower (P less than 0.05) and the fat content higher (P less than 0.01) in the paretic than in the non-paretic. This was relatively more pronounced in the arms than in the legs. We conclude that partial immobilization, owing to paresis after a cerebrovascular accident, results in characteristic changes in the affected limbs, with a marked decrease in the content of bone and lean tissue and a pronounced increase in fatty tissue.

Ischemic stroke in young adults I. Analysis of the etiological subgroups

Abstract: An ischemic stroke (IS) group including 386 patients under 50 years old is analysed taking into account different etiological subgroups and comparing risk factors against a control group of 100 people. The series points out the presence of 66.1% patients included in the inconclusive-atherothrombosis group, of which 22.7% had defined criteria of atheromatosis, while 11.6% were diagnosed of lacunar infarct. 13.5% of cases were considered as cardiac origin embolisms, and 14.1% were affected of mitral valve prolapse. The migraine group includes 4.9% of the patients while 17.6% belong to the miscellaneous group. The comparison of each of these groups with the control group showed significant differences for family history of stroke, personal history of peripheral arteriopathy, tobacco, arterial hypertension and previous IS.

Relationship between primitive reflexes, extra-pyramidal signs, reflective apraxia and severity of cognitive impairment in dementia of the Alzheimer type.

Abstract: — Controversy exists in the literature about the significance of primitive reflexes (PR) and extrapyramidal signs (EP) as diffuse cortical dysfunction signs and their relationship to age and cognitive impairment. A sample of 91 patients with a dementia of the Alzheimer type were examined with a standardized technique to assess the relationship between the finding of PR, EP and severity of cognitive impairment measured by Mini-Mental Status Examination. The value of a short cognitive test, the reflective apraxia (i.e imitation of meaningless gestures), were also assessed. A significantly lower MMS score was correlated with the number of present PR and with presence of snout, sucking and grasping reflexes. No correlation was found between presence or absence of PR and age, depression, or drug therapy. EP score was correlated with the number of present PR and MMS, but not with age. Reflective apraxia score was significantly correlated with the degree of cognitive impairment and was found with lower cognitive impairment than PR.