PURINE AND PYRIMIDINE NUCLEOTIDES IN THE BRAIN OF NORMAL AND CONVULSANT RATS

— Purine and pyrimidine nucleotides were measured in the brain of normal and electroshocked rats after chromatographic separation on ion-exchange resin of mono-, di- and tri-phosphorylated derivatives. CMP, IMP and NAD did not show any significant quantitative change. Adenine nucleotides showed an abrupt change followed by a rapid return to the control value. GTP was the only purine nucleotide exhibiting a relatively slow return to its starting concentration. The greatest percentage increase after electroshock was observed in UMP, which returned to its control value only after 5 min; UDPCoenzymes (i.e. UDPA plus UDPG) showed a relatively small drop during the development of the seizure and …

A caspase-3-dependent pathway is predominantly activated by the excitotoxin pregnenolone sulfate and requires early and late cytochrome c release and cell-specific caspase-2 activation in the retinal cell death

This study investigates the implication of mitochondria- and caspase-dependent pathways in the death of retinal neurones exposed to the neurosteroid pregnenolone sulfate (PS) shown to evoke apoptosis and contribute to amplification and propagation of excitotoxicity. After a brief PS challenge of intact retinas, caspase-3 and caspase-2 activation and cytochrome c release occur early and independent of changes in the oxidative state measured by superoxide dismutase activity. The temporal and spatial relationship of these events suggests that a caspase-3-dependent pathway is activated in response to cytochrome c release and requires caspase-2 activation and a late cytochrome c release in speci…

Great Auricular Neuralgia:

LEVITIRACETAM IN THE TREATMENT OF CREUTZFIELDT-JACOB DISEASE

High frequency of motoneuron dysfunction in FTD: a clinical and electrophysiological study

Pregnenolone sulfate, a naturally occurring excitotoxin involved in delayed retinal cell death.

The present study was designed to investigate the neurosteroid pregnenolone sulfate (PS), known for its ability to modulate NMDA receptors and interfere with acute excitotoxicity, in delayed retinal cell death. Three hours after exposure of the isolated and intact retina to a 30-min PS pulse, DNA fragmentation as assessed by genomic DNA gel electrophoresis and a modified in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method appeared concurrently with an increase in superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) levels. At 7 h, the increased amount of DNA laddering was accompanied by a higher number of TUN…

Back to the life: a case of tretable dementia

Binding of flunitrazepam to differentiating neurons cultured in a chemically defined, hormone-supplemented medium

[3H]Flunitrazepam (FNZ) binding to cortical neurons from fetal rat brain was investigated in vitro. The use of a synthetic medium specific for neurons made it possible to plot a developmental curve of3H-FNZ binding in an almost pure neuronal culture. Detectable specific binding was present in vitro at time 0 (that is, the 16th gestational day). A progressive increase of binding, due to an increment in the number of recognition sites, was observed on the subsequent days. The affinity of the specific binding sites to3H-FNZ was enhanced by the addition of exogenous GABA, whereas the density was not affected. © 1990 Plenum Publishing Corporation.

EXPRESSION OT THE CYSTINE/GLUTAMATE EXCHANGER IN THE RAT BRAIN

VALIDATION OF THE GUIDELINES FOR THE DIAGNOSIS OF DEMENTIA AND ALZHEIMER’S DISEASE OF THE ITALIAN NEUROLOGICAL SOCIETY. STUDY IN 72 ITALIAN NEUROLOGICAL CENTRES AND 1549 PATIENTS

PRIMARY PROGRESSIVE CROSSED APHASIA IN A DEXTRAL WOMAN

Pregnenolone sulfate modulates NMDA receptors, inducing and potentiating acute excitotoxicity in isolated retina

Pregnenolone sulfate (PS) acts as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptor-mediated responses. In the retina, we previously observed that the synthesis of pregnenolone and PS increases after stimulation of NMDA receptors and blockade of the synthesis reduces retinal cell death. This study was carried out to explore in the isolated and intact retina the possible role of PS in NMDA-induced excitotoxicity. Lactate dehydrogenase (LDH) measurements and morphological analysis revealed that a 90-min exogenous application of PS at 0.1-500 microM concentrations potentiated NMDA-induced cell death and at 50-500 microM concentrations caused cytotoxicity. After 45 min, ei…

Pancreatic encephalopathy: a 7-year follow-up case report and review of the literature

Pancreatic encephalopathy is a rare complication of acute pancreatitis. Clinical features include focal neurological signs and acute onset of dementia. This picture can fluctuate over time: cyclic progression with remission and relapses has been described. We present the case of a 43-year-old man who, after an acute episode of pancreatitis, experienced five relapses, with alternating focal signs. The patient has improved, but cognitive impairment persists after a 7-year follow-up.

ITALIAN NEUROLOGICAL SOCIETY GUIDELINES FOR THE DIAGNOSIS OF DEMENTIA: REVISION 1

THE PALMOMENTAL REFLEX IN AMYOTROPHIC LATERA SCLEROSIS

Differential effect of beta-N-oxalylamino-L-alanine, the Lathyrus sativus neurotoxin, and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate on the excitatory amino acid and taurine levels in the brain of freely moving rats.

We studied the effect of beta-oxalylamino-L-alanine, a glutamate analog present in Lathyrus sativus seeds and implicated in the etiopathogenesis of neurolathyrism, and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate on the extracellular levels of aspartate, glutamate and taurine in the primary motor cortex of freely moving rats. We found that while both neurotoxins increase the level of aspartate and glutamate, only (+/-)-alpha(-amino-3-hydroxy-5-methylisoxazole-4-propionate is able to modulate the level of taurine. GYKI-52466, a non-competitive non-NMDA antagonist, inhibited beta-oxalylamino-L-alanine-induced increase of aspartate, but not that of glutamate. Conversely, this ant…

Levetiracetam, a new option Treatment for Creutzfeldt-Jacob Disease.

A novel mutation (Thr116IIe) in the presenilin 1 gene in a patient with early-onset Alzheimer's disease

We report a novel presenilin 1 (PSN1) mutation (Thr116Ile) in a woman with early onset Alzheimer's disease (AD). This mutation was not found in 100 healthy controls, indicating that this is not a common polymorphism. The patient presented with forgetfulness at age 45, followed over the next 3 years by a worsening of the memory loss and frequent episodes of confusion and spatial disorientation. Neuroimaging studies were consistent with AD. The analysis of the family's pedigree showed that the proband was apparently the only member affected. Because the early death of several close relatives (i.e. the mother and the grandmother) and the demonstration that the father is not a mutation carrier,…

SISTEMA NEUROVEGETATIVO; PATOLOGIA E NOTE DI TERAPIA

EFFECT OF A MULTIDISCIPLINARY ALS CLINIC ON NIV TOLERANCE AND SURVIVAL IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS AND BULBAR IMPAIRMENT: A PROSPECTIVE STUDY

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DIABETIC THORACIC POLYRADICULOPATHY: A CASE WITH CLINICAL IMPROVEMENT FROM INTRAVENOUS IMMUNOGLOBULIN.

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Interaction Between Uridine and GABA-Mediated Inhibitory Transmission: Studies In Vivo and In Vitro

Na+-independent [3H]gamma-aminobutyric acid (GABA) binding to membrane preparations from frontal cortex, hippocampus, and thalamus is competitively inhibited by the in vitro addition of a naturally occurring pyrimidinic compound, uridine. Moreover, the intraperitoneal injection of uridine produces a dose-related decrease in the cerebellar content of cyclic GMP and antagonizes its increase elicited by bicuculline. The pyrimidinic compound also shows an antagonism toward bicuculline-induced seizures. The relationship between the anti-convulsant actions of uridine and GABA-mediated inhibitory neurotransmission is discussed in terms of an activation of GABA receptor function by the naturally oc…

Neuroscienze

Prolonged and intensive monitoring after starting non-invasive ventilation improves tolerance in patients with amyotrophic lateral sclerosis.

URIC ACID LEVELS IN SERUM AND CSF OF ALS PATIENTS

Objective: Urate (UA) is a potent antioxidant that effectively scavenges reactive nitrogen and oxygen radicals, and persons with a high plasma UA level may be at lower risk of some neurodegenerative disorders, as Parkinson’s disease (PD). Low plasma UA level has been observed in Alzheimer’s disease (AD) and vascular dementia, but there is no data on correlations to neuropsychological test results in these patient groups. Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron disease, with a highly variable rate of progression and whose diagnosis is chiefly based on clinical and neurophysiological parameters. The etiopathogenesis is unknown, but the oxidative stress seems to play …

Chronic inflammatory demyelinating polyneuropathy presenting as isolated unilateral ptosis and adduction deficit

Cerebral Venous Sinus Espansion in Post Puncture Headache

THE COGNITIVE AND BEHAVIOURAL IMPAIRMENT IN AMYOTROPHIC LATERAL SCLEROSIS

Interaction of uridine with GABA binding sites in cerebellar membranes of the rat

The effect of uridine, a postulated anticonvulsant agent, on GABA receptors has been investigated. Uridine inhibits [3H]GABA binding to rat cerebellar buffer-washed membranes. Pretreatment of the membranes with Triton X-100 increases the effect of uridine on GABA-binding. The Scatchard analysis reveals that both high and low affinities of GABA for its receptors are affected by 1 mM uridine, while the apparent number of binding sites remains unchanged. The ability of uridine to interact competitively with GABA binding sites, also examined by the Lineweaver-Burk analysis, suggests a possible mechanism of action of this anticonvulsant agent, so including it among those compounds characterized …

Electroretinographic response in WAG/Rij rats after low-intensity cyclic light exposure.

In order to investigate the combined influence of age and light, the b-wave and oscillatory potentials (OPs) of the electroretinogram (ERG) were recorded in 1.5-, 7- and 12-month-old WAG/Rij rats, reared under homogenous low-intensity cyclic light exposure. Wistar albino rats of the same ages, reared under the same conditions, served as controls. The b-wave amplitude decreased, and its implicit time increased in the older age groups significantly more in WAG/Rij than in Wistar rats. Statistical analysis indicated that the b-wave amplitude is a more suitable parameter than implicit time in differentiating the ERG variations of one rat strain from the other. The added amplitude of the OPs als…

PROLONGED AND INTENSIVE MONITORING AFTER STARTING NON-INVASIVE VENTILTION IMPROVES TOLERANCE IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS.

Progressive visuospatial dysfunction as a clinical entity.

Restless legs syndrome in patients with amyotrophic lateral sclerosis

We aimed to evaluate the frequency and determinants of restless legs syndrome (RLS) in a group of 76 patients with amyotrophic lateral sclerosis (ALS) and 100 control subjects. A diagnosis of RLS was made according to the criteria of the International RLS Study Group, and severity was assessed by the RLS severity scale. RLS was significantly more frequent in patients with ALS (ALS/RLS(+)) than in control subjects (25% vs. 8%; P = 0.002). Compared with control subjects, patients with ALS/RLS(+) showed shorter history of RLS complaints and higher frequency of symptoms occurrence. Moreover, compared with those without RLS, patients with ALS/RLS(+) showed increased functional impairment and mor…

Effect of beta-N-oxalylamino-L-alanine on cerebellar cGMP level in vivo.

Beta-N-oxalylamino-L-alanine (BOAA), a non-protein amino acid present in the seeds of Lathyrus Sativus (LS), is one of several neuroactive glutamate analogs reported to stimulate excitatory receptors and, in high concentrations, cause neuronal degeneration. In the present study, the in vivo acute effects of synthetic BOAA and LS seed extract were investigated on rat cerebellar cyclic GMP following intraperitoneal (10-100 mg/kg) or oral (100 mg/kg) administration of subconvulsive doses of toxin. Furthermore, the BOAA content in LS seeds and in the cerebellum of injected rats was determined by high performance liquid chromatograph analysis. A dose- and time-dependent increase of cerebellar cy…

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: effect on survival.

Abstract Background Percutaneous endoscopic gastrostomy (PEG) is offered to amyotrophic lateral sclerosis (ALS) patients with severe dysphagia. Immediate benefits of PEG are adequate food intake and weight stabilization. However, the impact of PEG on survival is still uncertain. In this work we retrospectively evaluated the effect of PEG on survival in a cohort of ALS patients followed in a tertiary referral centre. Methods Between 2000 and 2007, 150 dysphagic ALS patients were followed until death or tracheostomy. PEG was placed in 76 patients who accepted the procedure and survival was analysed using the Kaplan–Meier life-table method. Results In ALS patients submitted to PEG, no major co…

NON-INVASIVE VENTILATION IN AMYOTROPHIC LATERAL SCLEROSIS: A RETROSPECTIVE STUDY

Human neuroblastoma SH-SY5Y cell line: neurosteroid-producing cell line relying on cytoskeletal organization.

Pregnenolone, the precursor of all steroids, is synthesized by CNS structures. The synthesis requires an obligatory step involving cholesterol transport to mitochondrial cytochrome P450-cholesterol side chain cleavage (cytP450scc), although the underlying mechanism(s) are still mostly unknown. We used the human neuroblastoma SH-SY5Y cell line to investigate cytP450scc expression and activity and to establish a role of cytoskeleton in pregnenolone synthesis. Immunocytochemical and biochemical approaches revealed that undifferentiated as well as differentiated cells either by retinoic acid (RA) or phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), possess cytP450scc and rapidly synthes…

EVALUATION OF PROGRESSION IN AMYOTROPHIC LATERAL SCLEROSIS: A NEUROPHYSIOLOGICAL APPROACH

Expression and developmental regulation of the cystine/glutamate exchanger (xc-) in the rat.

The cystine/glutamate exchanger (antiporter x c − ) is a membrane transporter involved in the uptake of cystine, the rate-limiting amino acid in the synthesis of glutathione. Recent studies suggest that the antiporter plays a role in the slow oxidative excitotoxity and in the pathological effects of β-N-oxalylamino-l-alanine, the molecule responsible for neurolathyrism, a neurotoxic upper motor neuron disease. The mouse cystine/glutamate exchanger has been cloned and showed to be composed of two distinct proteins, one of which being a novel protein, named xCT, of 502 amino acids and 12 putative trans-membrane domains. We have generated and purified a polyclonal antibody to mouse xCT and stu…

Acute reversible parkinsonism in a diabetic-uremic patient.

Acute movement disorders with basal ganglia lesions have been recently described in diabetic-uremic patients of Asian descent. The process is often reversible, with a favourable clinical outcome. Metabolic (i.e. uremic toxins) and microangiopathic changes have been suggested to be involved in its pathophysiology, even though racial and/or genetic factors might play a role too. In this report, we present a Caucasian diabetic patient with a long-lasting mild uremia in which acute parkinsonism occurred after a steep and unexpected increase of the serum creatinine. The follow-up demonstrated a significant improvement of the neurological signs and symptoms, the creatinine level lowered close to …

EXPRESSION OF THE CYSTINE/GLUTAMATE EXCHANGER IN THE RAT BRAIN

SCA17 AS CAUSE OF EARLY-ONSET DEMENTIA IN SOUTHERN ITALY: REPORT OF A NEW FAMILY

NON - INVASIVE VENTILATION IN AMYOTROPHIC LATERAL SCLEROSIS: A RETROSPECTIVE STUDY

PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) IMPROVES SURVIVAL IN AMYOTROPHIC LATERAL SCLEROSIS

Lateral differences in GABA binding sites in rat brain.

An asymmetric distribution of GABA binding sites was found in the cerebral cortex, hippocampus, cerebellar hemispheres, striatum, and thalamus. Higher levels of [3H]GABA binding were observed in the left-side of most brain areas and in a greater percentage of adult rats, but the opposite asymmetry was found in the thalamus. A similar left-right difference in cerebral hemispheres was also found in five day-old rats, suggesting the genetic predetermination of asymmetry.

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

Objectives - To determine the causes and place of death in a cohort of Italian patients with amyotrophic lateral sclerosis (ALS). A better understanding of the likely causes of death in ALS might improve the palliative care at the end-of-life, whereas knowing the place of death will help to verify the need for highly specialized care services, e.g. hospice and nursing home. Patients and methods - Between 2000 and 2008, 182 ALS patients (onset: spinal, 127; bulbar, 55; M/F: 1.6) were followed in a single ALS Tertiary Centre in Palermo, Sicily, Italy until death. Medical data for each individual patient were recorded in a large database throughout the disease course. Information concerning ca…

Cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis with EDSS ≤ 3.5

Objectives – Previous papers have mainly demonstrated the presence and the frequency of cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis. The purpose of this study was to investigate subjects with the relapsing-remitting form of the disease and mild clinical disability (EDSS ≤ 3.5), so as to quantify this deficit when the illness does not yet interfere with daily living and the ability to work. Methods – Fifty patients and 50 healthy controls were submitted to a wide neuropsychological battery, including Wechsler Memory Scale – I- (WMS), Benton Visual Retention Test – D- (BVRT), Raven Coloured Progressive Matrices (RCPM), Kohs’ test (KT), Judgement of L…

RESTLESS LEGS SYNDROME IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS: A CASE-CONTROL STUDY.

Therapeutic considerations in cerebellopontine angle lipomas inducing hemifacial spasm.

Lipoma is a very rare tumour at the cerebellopontine angle. We report a case of incomplete hemifacial spasm, associated with a lipoma involving and compressing both facial and acoustic nerves at their origin in the brainstem. The patient was treated with medical therapy (botulinum toxin A) and surgery. We present a review of the last ten years of the literature, with particular regard to management.

THE VALUE OF PHYSICAL AND OCCUPATIONAL THERAPY FOR PATIENTS WITH ADVANCED MOTOR NEURON DISEASE (MND) AND SEVERE MOTOR AND FUNCTIONAL IMPAIRMENT

Neurosteroidogenesis in Rat Retinas

Neurosteroids (steroids synthesized in the CNS) function by modulating neurotransmission. To establish an experimental model for investigation of neurosteroid synthesis and regulation, independent of blood-borne steroids, we examined the steroidogenic activity of isolated rat retinas. We identified progesterone, pregnenolone, dehydroepiandrosterone, desoxycorticosterone, 3 alpha,5 alpha-tetrahydrodesoxycorticosterone, 3 alpha-hydroxy-5 alpha-dihydroprogesterone, 17-hydroxyprogesterone, and 17-hydroxypregnenolone together with their esterified forms. As pregnenolone is the precursor of all steroids, its formation was studied in detail as an index of a steroid-synthesizing tissue. Pregnenolon…

Incidence and prevalence of amyotrophic lateral sclerosis in Sicily: a population based study

LA DISFUNZIONE RESPIRATORIA NELLA SCLEROSI LATERALE AMIOTROFICA

ESPRESSIONE DELL’ANTIPORTER CISTINA/GLUTAMMATO XC- NEL SISTEMA NERVOSO DI RATTO

Legal and assistance aspects of Alzheimer's disease: analysis of 100 cases.

Caring for patients with disabling cognitive diseases, such as Alzheimer's disease (AD) and other progressive dementias, has a number of legal and social welfare implications. The two main problems to be discussed with patients and caregivers are the need for a legal guardian and requests for government financial support, both of which depend on the patient's progressive loss of autonomy and increasing need for assistance. In order to study the presence of these two support measures, we considered 100 AD patients (56 women and 44 men) divided in four groups on the basis of the stage of the disease: mild (25), moderate (34) and severe (32), or death (9). We investigated the number of caregiv…

MALATTIE DEL TRONCO DELL’ENCEFALO

Induction of neurosteroid synthesis by NMDA receptors in isolated rat retina: a potential early event in excitotoxicity

Here we investigated the possible regulation of neurosteroidogenesis by N-methyl-D-aspartic acid (NMDA) receptor activation and addressed the hypothesis that neurosteroid synthesis may be involved in acute excitotoxicity. In the isolated retina, exposure to NMDA modified pregnenolone and pregnenolone sulphate formation. This effect was dose and time dependent, the synthesis being increased by relatively moderate NMDA doses (1-100 microM) within 30 min exposure and reduced to its control value by 60 min or by raising drug concentrations. NMDA-stimulated neurosteroid synthesis was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) and 3(2-ca…

Isolate progressive visuospatial dysfunction: a new form of MCI?

Neurosteroids in the Retina

Steroids may have a powerful role in neuronal degeneration. Recent research has revealed that steroids may influence the onset and progression of some retinal disorders as well as neurodegenerative diseases and, as in brain, they accumulate in the retina via a local synthesis (neurosteroids) and metabolism of blood-circulating steroid hormones. Their crucial role as neurodegenerative and neuroprotective agents has been also upheld in a retinal excitotoxic paradigm. These findings are reviewed especially from the emerging perspective that after an insult local changes in steroidogenic responses and consequent neurosteroid availability might turn out to be offensive or defensive cellular adap…

Memoria

gamma-Aminobutyric acid type A/benzodiazepine receptors regulate rat retina neurosteroidogenesis.

Abstract It has been previously shown that retinal ganglion cells have the ability to synthesize steroids including neuroactive steroids such as pregnenolone sulfate. Since ganglion cells possess GABAA/benzodiazepine (BZ) receptors and neurosteroids modulate retinal GABAA receptor function, we investigated the role of these receptors in isolated rat retina neurosteroidogenesis. Ligands for central-type BZ receptors stimulated retinal pregnenolone synthesis. Clonazepam was the most potent ligand examined acting at nanomolar concentrations. Moreover, the effective steroidogenesis stimulatory dose (ED50) for these ligands and theKi to inhibit [3-H]flunitrazepam binding showed a coefficient of …

Changes in Cerebral Amino Acid Transport During Development

The transport of metabolites to and from the central nervous system is of considerable interest. To a greater extent than most other tissues, central nervous system tissue invitro takes up amino acids to well above their concentrations in the incubation medium. Presumably the transport systems responsible for this uptake and for efflux invitro are also those responsible for transport between brain cells in living animals2.

PROLONGED AND INTENSIVE MONITORING AFTER STARTIN NON-INVASIVE VENTILATION IMPROVES TOLERANCE IN PATIENT WITH AMYOTROPHIC LATERAL SCLEROSIS

OROPHARINGEAL CARCINOMA MIMIKING BULBAR ONSET AMYOTROPHIC LATERAL SCLEROSIS

Levetiracetam in the Treatment of Creutzfeldt-Jacob Disease.

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

Objectives - To determine the causes and place of death in a cohort of Italian patients with amyotrophic lateral sclerosis (ALS). A better understanding of the likely causes of death in ALS might improve the palliative care at the end-of-life, whereas knowing the place of death will help to verify the need for highly specialized care services, e.g. hospice and nursing home. Patients and methods - Between 2000 and 2008, 182 ALS patients (onset: spinal, 127; bulbar, 55; M/F: 1.6) were followed in a single ALS Tertiary Centre in Palermo, Sicily, Italy until death. Medical data for each individual patient were recorded in a large database throughout the disease course. Information concerning ca…

Common risk factors of three diseases.

INDIVIDUAL AND HEALTH-RELATED QUALITY OF LIFE ASSESSMENT IN AMYOTROPHIC LATERAL SCLEROSIS PATIENTS AND THEIR CAREGIVERS

Abstract: We performed a cross-sectional study aimed to address the quality of life (QoL) and putative associated variables in amyotrophic lateral sclerosis (ALS) patients and their respective caregivers, using both health-related (WHOQOL-BREF) and individual (SEIQoL-DW) QoL instruments. Further, we sought to investigate concordance within patient-caregiver pairs for ratings of respective QoL. Thirty-seven patient-caregiver pairs were included in the study. QoL was rated low by both patients and caregivers, and there was no significant difference between them on scores of overall QoL, even if caregivers showed higher scores on the physical and psychological WHOQOL-BREF domains compared to p…

Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival.

Objective: To identify factors associated with tolerance and survival after noninvasive positive-pressure ventilation (NIPPV) and to investigate the influence of NIPPV on lung function in patients with ALS. Methods: NIPPV was offered to 71 patients with ALS in accordance with currently published guidelines. Effects of NIPPV on lung function and factors influencing tolerance and survival after NIPPV were studied. Results: Forty-four patients (61.9%; 95% CI: 50.6 to 73.2) tolerated NIPPV (NIPPV use >= 4 h/day) and 27 (38.1%; 95% CI: 26.8 to 49.4) were intolerant (NIPPV use = 4 h/day) and to the modifications of forced vital capacity decline after treatment initiation. The severity of bulbar i…

Cerebrospinal fluid tau protein is not a biological marker in amyotrophic lateral sclerosis.

Background:  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau, an axonal microtubule-associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others. Methods:  Total CSF tau level was assayed in a population of ALS patients (n = 57) and controls (n = 110) using a specific ELISA method. Results:  No significant differences in the median CS…

NEUROPHYSIOLOGIC AND CLINICAL SIGNS OF MOTONEURONAL DEGENERATION IN FRONTOTEMPORAL DEMENTIA

Lateral differences in the GABAergic system of the rat striatum.

Asymmetric differences have been found in the pre- and postsynaptic activity of the GABAergic system of the left and right striata of the rat. 3H-GABA binding shows a higher dissociation constant (KD) and a higher number of sites (Bmax) in the left striatum than in the right. Moreover, 3H-diazepam binding seems to be more extensively activated by GABA in the right striatum suggesting a more sensitive postsynaptic GABAergic activity than on the left side. However, when the presynaptic marker (GAD activity) was measured, the asymmetry was in the opposite direction. The results provide further neurochemical evidence of the functional asymmetry of the rat brain.

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis

Background: Percutaneous endoscopic gastrostomy (PEG) is offered to amyotrophic lateral sclerosis (ALS) patients with severe dysphagia. Immediate benefits of PEG are adequate food intake and weight stabilization. However, the impact of PEG on survival is still uncertain. In this work we retrospectively evaluated the effect of PEG on survival in a cohort of ALS patients followed in a tertiary referral centre. Methods: Between 2000 and 2007, 150 dysphagic ALS patients were followed until death or tracheostomy. PEG was placed in 76 patients who accepted the procedure and survival was analysed using the Kaplan-Meier life-table method. Results: In ALS patients submitted to PEG, no major complica…

NONINTENSIVE POSITIVE-PRESSURE VENTILATION IN ALS.

ACUTE REVERSIBLE PARKINSONISM IN A DIABETIC UREMIC PATIENT

Development of chronic hypoventilation in amyotrophic lateral sclerosis patients

SummaryEarly prediction of respiratory muscle involvement and chronic hypoventilation (CH) in amyotrophic lateral sclerosis (ALS) patients can help to plan mechanical ventilatory aids and palliative care interventions well before respiratory failure occurs. To describe the natural history of the progressive pulmonary dysfunction leading to CH, and to identify potential parameters associated with its development in ALS, we prospectively followed 38 ALS patients up to 26 months, starting from their first presentation at our Clinic. At study entry, median FVC was 87% (interquartile range: 72–104%) and declined by 10% after 6 months (range: 2–49%), showing a very high inter-patient variability.…

Variant Creutzfeldt-Jakob disease in an Italian woman.

Summary As of May, 2002, 128 cases of variant Creutzfeldt-Jakob (vCJD) disease have been identified in the UK, France, and Ireland. We report the first case of vCJD in Italy. The patient was a young Italian woman who had never travelled to a country with bovine spongiform encephalopathy (BSE). She was diagnosed by cerebral MRI and western blot analysis of tonsil biopsy samples. The results of these analyses suggest that vCJD in continental Europe and the UK share genetic, clinical, and neuroimaging features, with similar western blot patterns. The identification of vCJD in Italy could have important implications for public-health policy decisions and clinical surveillance in Italy and other…

Dysembryoplastic Neuroepithelial Tumor of the Brainstem

Dysembryoplastic neuroepithelial tumor (DNT) is a clinically benign stable lesion, most frequently located in the temporal and frontal lobes, often responsible for epilepsy in young adults. We describe an unusual case of DNT in the brainstem of a 45-year-old woman. Brain MRI showed a multicystic-like lesion localized in the left inferior pons, involving the ipsilateral cerebellar peduncle and partially dislocating the fourth ventricle. The specific pattern of MRI and CT appearance of DNT and its benign course (our patient is clinically stable with unchanged MRI images at two year follow-up) may help differentiate this tumor from other lesions, i.e. ganglioglio-mas and glioneural malformati…

THE “CROSS SIGN” FREQUENCY IN A LARGE SERIES OF NEUROLOGICAL PATIENTS

HOMOZIGOUS DJ-1 MUTATION IN A FAMILY FROM SOUTHERN ITALY WITH AMYOTROPHIC LATERAL SCLEROSIS-PARKINSONISM-DEMENTIA COMPLEX

Tumor necrosis factor alpha polymorphism C-850T is not associated with Alzheimer's disease and vascular dementia in an Italian population.

A pathogenic role of inflammatory factors has been proposed both in Alzheimer's disease (AD) and vascular dementia (VD). A previous report indicated the presence of polymorphism C-850T of tumor necrosis factor (TNF) alpha as a genetic risk factor for VD and, associated with apolipoprotein E epsilon 4, for AD. We have assessed the association between TNF-alpha polymorphism and dementias in Italian populations of AD, VD and elderly controls. The influence of TNF-alpha polymorphism on dementia has not been confirmed in this segment of the Italian population.

How specific are the pontine MRI hyperintensities (the cross sign)?

PREDICTORS OF SURVIVAL AFTER NON - INVASIVE POSITIVE - PRESSURE VENTILATION IN ALS PATIENTS

MALATTIE DEL MIDOLLO SPINALE

A cervical myelopathy with a Hirayama disease-like phenotype

A 21-year-old man with a muscular atrophy of the left distal upper extremity is presented. The disorder had been progressive over a few years, showing an exacerbation of the hand's weakness when the patient worked in a chilled environment (i.e., in a cold room). The patient's diagnostic work-up was extensive and the MRI documented the presence of a cervical myelopathy, associated to an inversion of the physiological lordosis at the C5-C6 level, with a phenotype highly resembling Hirayama disease. This case indirectly supports the debated hypothesis that juvenile amyotrophy of the upper limb (Hirayama disease) is actually a type of cervical myelopathy, with a likely ischaemic pathogenesis of…

P3‐214: Identification of three novel progranulin mutations in a series of patients affected by sporadic and familial frontotemporal lobar degeneration

Is the focal signal hyperintensity within the capsula interna on MRI a marker of CST degeneration?

Amino acid transport in the retina.

The uptake, exit, homoexchange, inhibitory pattern, and kinetic analysis of transport of three amino acids were studied in the isolated retina of adult rat under different metabolic conditions. Only in the case of glycine, uptake and exit were shown to duplicate the processes observed in brain slices. In the case of lysine, glucose and oxygen showed an inhibitory effect, but with glutamate spontaneous exit could not be measured. It was also found that the rate of homoexchange for glycine and glutamate, but not for lysine, increases in the presence of oxygen and glucose.

l-[3H]lysine binding to rat retinal membrane: II. effect of kainic acid,d,l-?-aminoadipic acid, iodoacetic acid, and modification by dark-exposure

The rat retina and the different brain regions contain membranes sites that bindl-lysine in the nanomolar range. These binding sites undergo changes in different experimental conditions, thus: I) intraocular injection of kainic acid induces a reduction of the density ofl-lysine binding sites, II)d,l-α-aminoadipic acid injected into the eye enhances both kinetic parameters (Bmax andKd) ofl-[3H]lysine binding sites, III) the intraperitoneal injection of iodoacetic acid decreases the sensitivity for its ligand binding sites, and IV) the exposure to darkness of the rats reducesl-[3H]lysine binding in the retina, thalamus, hypothalamus and superior colliculus, but not in the occipital cortex; su…

Myasthenia gravis associated with Charcot-Marie-Tooth neuropathy: report of a case

We report the case of a 24 year old woman who developed myasthenia gravis in the course of a mild form of Charcot-Marie-Tooth neuropathy. We describe the clinical manifestations together with the neurophysiological, pathological, serological findings and response to therapy and discuss the unusual association in the light of the relevant literature. © 1992 Masson Italia Periodici S.r.l.

YOUNG PATIENT PRESENTING CEREBELLAR ATAXIA ASSOCIATED WITH ANTI-GAD ANTIBODIES. CASE REPORT AND HYPOTHESIS

CSF HOMOCYSTEINE LEVELS IN AMYOTROPHC LATERAL SCLEROSIS

CSF homocysteine levels in Amyotrophic Lateral Sclerosis

l-[3H]lysine binding to rat retinal membrane: I. Quantitative determination and characterization of the binding sites

A saturable reversible binding to membranes from rat retina has been found for L-[3H]lysine. Specific binding is time, temperature and protein concentration-dependent, and shows stereospecificity. The best computer fits of the experimental data are obtained with a receptor model based on two independent binding sites, of which only one site with a Kd value of 229.4 +/- 14.23 nM and a Bmax of 2.04 +/- 0.11 pmol/mg protein could be characterized satisfactorily. Several compounds included putative neurotransmitters have moderate or no affinity for L-lysine binding sites. A different pattern of distribution of L-[3H]lysine binding sites is observed among various regions of the brain, with the h…

Aspartate aminotransferase in brain tissue cultures

TELEPHONE FOLLOW-UP FOR PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

The relentless evolution of amyotrophic lateral sclerosis (ALS), a severe neurodegenerative disorder of the upper and lower motoneurons, leads to an increasing level of disability. Most patients, during the course of the disease, become unable to attend the tertiary clinical care center and are thus prevented from enrolling in clinical trials or benefiting from specialized care and management. The main objective of this study was to verify whether the ALS functional rating scale (ALSFRS) could be reliably administered by telephone to patients, when unable to attend the ALS clinic, or to their caregivers. ALSFRS is a validated instrument that assesses the functional status and the disease pr…

SERUM CREATINE KINASE LEVEL IN AMYOTROPHIC LATERAL SCLEROSIS: A USEFUL DIAGNOSTIC AID?

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Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results ofa multicentre, randomized, double-blind, placebo-controlled study

INTRODUCTION A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. PATIENTS AND METHODS Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to th…

FOCAL SIGNAL-INTENSITY VARIATIONS IN THE POSTERIOR ARM OF THE INTERNAL CAPSULE IN CONVENTIONAL MRI

DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.

Mutations in DJ-1 gene have been recently shown to cause autosomal recessive early-onset Parkinson’s disease (EOPD) in a large Dutch family and in a small consanguineous Italian family.1 Subsequent to this initial finding, several additional DJ-1 mutations were identified in subjects with EOPD.2–6 We describe a family from southern Italy with three brothers affected by a complex disorder characterized by early-onset parkinsonism-dementia-amyotrophic lateral sclerosis (EOPD-D-ALS). The analysis of the DJ-1 gene showed a novel homozygous mutation (E163K) in exon 7 and a novel homozygous mutation (g.168_185dup) in the promoter region of this gene in living affected subjects