Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis.

BACKGROUND: Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine (a mediator of inflammation implicated in the pathogenesis of multiple sclerosis-MS) in the CNS. We have investigated the possible association between a single nucleotide polymorphism of the HNMT (chromosome 2q22.1), that causes the amino acid substitution Thr105Ile (decreasing enzyme activity) and the risk for MS. METHODS: We studied the frequency of the HNMT genotypes and allelic variants in 228 MS patients and 295 healthy controls using a PCR-RLFP method. RESULTS: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. CONCLUSION: The HNMT polymorphism is not related with the risk for MS.

[The neurochemistry and neuropharmacology of diffuse Lewy body disease]. / Neuroquímica y neurofarmacología de la enfermedad difusa de cuerpos de Lewy.

INTRODUCTION AND DEVELOPMENT: The main neurochemical alteration in diffuse Lewy body disease (DLBD) is the cholinergic deficit in the cerebral cortex, which involves mainly cholin-acetyl-transferase. There have been also described dopamine deficiency and alterations affecting other neurotransmitters and neuromodulators, such as serotonin, noradrenaline, neuropeptides, etc. Cerebral perfusion and glucose metabolism studies usually show diffuse hypoperfusion or hypometabolism, with higher alteration of associative cortex, including occipital involvement. Several studies have shown increased markers of oxidative stress in brain and other tissues, suggesting its possible role in the pathogenesis of DLBD. CONCLUSIONS: Acetylcholinesterase inhibitors seem to improve cognitive and conductual symptoms, although their usefulness according evidence-based medicine criteria is weak. Some patients need atypical neuroleptics at low doses to get the symptomatic control of conductual alterations.

[The neurochemistry and neuropharmacology of frontotemporal dementia]. / Neuroquimica y neurofarmacologia de la demencia frontotemporal.

AIM: To review the neurochemical features and therapeutic options for frontotemporal dementia (FTD). DEVELOPMENT: The main neurochemical alterations in FTD are the serotoninergic and dopamine depletion. In contrast with Alzheimer's and diffuse Lewy bodies disease, there are not significant alterations of the cholinergic system. Cerebral perfusion and glucose metabolism studies usually show hypoperfusion or hypometabolism, with predominant involvement of temporal and frontal cortices. There have been described some alterations related with oxidative stress and apoptosis, although its pathogenetic role in FTD is not well known. Treatment of FTD is not well established, because there are only a few studies with some drugs. The most studied drugs are serotonin reuptake inhibitors, however, despite the well-known serotoninergic deficiency described in FTD, the results are not conclusive. CONCLUSIONS: The main neurochemical alterations of FTD are serotoninergic and dopaminergic deficiencies. The treatment is not well established, although it should be theoretically ideal to use drugs which modulate these neurotransmitter systems.

[Oxidative stress and Alzheimer's disease]. / Estrés oxidativo y enfermedad de Alzheimer.

INTRODUCTION: According to the oxidative stress hypothesis, the pathogenesis of several diseases should be related with an excessive production of prooxidant substances (free radicals, transition metals), the deficiency of antioxidant defensive mechanisms, or both. Oxidative stress has been implicated in the pathogenesis of aging of the brain and several neurological diseases, including Alzheimer's disease (AD). DEVELOPMENT: In recent years there are many data suggesting a possible role of oxidative stress in the pathogenesis of AD. These include the demonstration of increased oxidation of lipids, proteins and deoxyribonucleic acid, alterations in mitochondrial function and the possible role of amyloid beta and its precursor protein in the oxidative reactions in experimental models (cortical neuronal cultures and transgenic animals). CONCLUSIONS: Many studies show increased oxidative stress in the brain of patients with AD, although its possible role con the pathogenesis of this disease are controversial.

Tau protein concentrations in cerebrospinal fluid of patients with multiple sclerosis.

UNLABELLED: FUNDAMENTALS AND OBJECTIVE: Multiple sclerosis (MS) is the prototype of demyelinating disease, but recently, it has been shown that the existence of axonal lesions contribute to irreversible central nervous system damage in this disease. Tau proteins are considered to be important for maintaining the stability of axonal microtubules involved in the mediation of fast axonal transport of synaptic constituents. There have been reports of increased cerebrospinal fluid (CSF) tau concentrations in patients with MS, and it has been suggested that this could be a marker of axonal damage. The objective of the present study was to elucidate whether CSF tau levels could be a marker of MS activity. PATIENT AND METHODS: We measured tau concentrations in the CSF of 20 patients with MS (nine in the first, seven in the second, one in the fourth exacerbation, and three patients with chronic progressive course) and 32 age- and sex-matched controls, using a specific enzyme-linked immunosorbent assay method. RESULTS: The CSF tau concentrations of patients with MS did not differ from those of controls, and they were not correlated with age at onset and duration of the disease. CONCLUSION: CSF tau concentrations are not a marker of MS activity.

[Symptomatic treatment of multiple sclerosis]. / Tratamiento sintomático de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis is a chronic neurological disorder which affects middle aged adults. It usually means serious physical, psychological, social and employment problems for the patients concerned. METHOD: From the anatomo pathological point of view, it is characterized by demyelination and axon damage in the central nervous system. The clinical features are variable, depending on the course of the disease, its clinical form and the sites of the lesions. Symptoms may appear in bouts, as relapses of the disorder or as a result of incomplete recovery from these episodes and cause severe disability. CONCLUSION: We review the physiopathology and most widely used treatment for management of the commonest symptoms of multiple sclerosis.

Cerebral lymphoma presenting as a leukoencephalopathy.

Cerebral lymphoma is infrequent in immunocompetent patients. This tumour usually appears on CT and MRI as a single lesion or as multiple lesions with mass effect and homogeneous enhancement after contrast administration. A patient is described with a cerebral lymphoma, confirmed by histopathological examination, who presented as a progressive leukoencephalopathy.

[Respiratory form of onset of motor neuron disease]. / Forma de comienzo respiratorio de la enfermedad de motoneurona.

OBJECTIVE: To present a case of respiratory failure as the form of onset of amyotrophic lateral sclerosis, to review the main clinical findings, data of the investigations done which suggest the presence of this disorder and describe its therapeutic management. CLINICAL CASE: A 68 year old man presented with a subacute illness characterized by a sleep disorder with sleep fragmentation, snoring of increasing intensity, without clear pauses of apnea, progressive diurnal hypersomnia accompanied by progressive dyspnea followed by respiratory failure with respiratory acidosis and difficulty in manipulating things with his hands. Diagnostic investigations showed a restrictive pattern without pulmonary fibrosis, due to paralysis of the diaphragm, and the presence of electromyographic signs compatible with motorneuron disease. The patient was treated with riluzole 100 mg/day and non-invasive mechanical ventilation and maintained an acceptable quality of life. CONCLUSIONS: Motorneuron disease may start with acute or progressive respiratory failure without a clear etiological cause and may appear to be similar to obstructive sleep apnea syndrome. The treatment of choice for this respiratory problem is non-invasive mechanical ventilation. Absence of symptoms of bulbar involvement is essential for a favourable prognosis.

[Do antioxidants in the diet affect the risk of developing Parkinson disease?]. / Influyen los antioxidantes de la dieta en el riesgo para desarrollar enfermedad de Parkinson?

OBJECTIVE: A number of studies suggest the existence of 'oxidative stress' in the substantia nigra from parkinsonian patients. If 'oxidative stress' should be relevant in the pathogenesis of Parkinson's disease (PD), the consumption of antioxidant or prooxidant substances in the diet could theoretically influence the risk for this disease. DEVELOPMENT: A critical up to date review of the literature regarding premorbid consumption of antioxidants or prooxidants by PD patients and controls has been done. Most studies have been retrospective, they have been performed following different designs, and disclosed contradictory results. CONCLUSION: From the current literature, it is unlikely that dietetic consumption of prooxidants and antioxidant, specially vitamin E (the most frequently studied antioxidant) have any influence on the risk for PD.

[Brown-Séquard syndrome as the initial clinical manifestation ofmultiple sclerosis]. / Síndrome de Brown-Séquard como primera manifestación clínica de esclerosis múltiple.

Multiple sclerosis is a disorder with different forms of clinical presentation. The Brown-Séquard syndrome has occasionally been described in association with multiple sclerosis. We present the case of a patient whose initial clinical presentation of multiple sclerosis was the Brown-Séquard syndrome.

Symptomatic orthostatic tremor in pontine lesions.

Orthostatic tremor (OT) is a rare movement disorder that consists of involuntary shaking of the legs and trunk present only on standing. Although the origin and the mechanism of this condition are not well understood, the neurophysiologic abnormalities and PET studies suggest a central origin. We describe the clinical and radiologic features of two patients with symptomatic OT and associated pontine lesions, and conclude that OT may arise from dysfunction of the cerebellum or related pontine structures.

Premorbid dietetic habits and risk for Parkinson's disease.

To evaluate the possible role of antioxidant (vitamins A, E, C, beta-carotene, zinc, selenium) or pro-oxidant (iron, copper, manganese) factors present in the diet, in the risk for Parkinson's disease (PD), we conducted a dietetic study (pre- and postmarriage) which included 91 foodstuffs. We interviewed separately 119 PD patients (64 males, 55 females, age 65.3 +/- 8.5 years, age at marriage 27.8 +/- 5.9 years) and their spouses (age 65.0 +/- 9.2 years, age at marriage 27.2 +/- 5.9 years) as the control group (C). Premarriage consumption for each foodstuff was classified into: (1) rarely of annually, (2) monthly, or (3) weekly; and postmarriage consumption (which included the period between age at marruage and age 40 years; only concordant answers were considered to be valid) into: (1) PD > Control, (2) Control > PD, and (3) PD = Control. The premarriage interview showed a trend towards a lower consumption of peas in PD patients as compared to controls. The postmarriage interview in PD patients showed a higher tendency for the consumption of rice, bluefish, liver paté and eggs, and a less consumption of tea than controls. We were unable to find any consistent trend towards a lower consumption of vitamins E and C during adulthood in PD patients, but they seemed to have eaten selenium-rich foodstuffs more frequently than controls. These results differ from those obtained by previous studies, and question the possible role of premorbid dietary habits on the risk for PD.

Drug-induced parkinsonism in a movement disorders unit: A four-year survey.

UNLABELLED: To establish the frequency of drug-induced parkinsonism (DIP) and the drugs responsible for this side-effect we reviewed the database of our Movement Disorders Unit during the first 4 years of its use. The diagnostic criteria for DIP included: (1) the presence of two or more cardinal symptoms of parkinsonism, (2) an absence of parkinsonian symptoms before the exposure to the offending drug, (3) a disappearance or significant improvement in parkinsonism after withdrawal of the offending drug, (4) no better explanation for the parkinsonism. One-hundred and five patients fulfilled the diagnostic criteria for DIP (16.3% of total patients referred and 33.8% of patients with parkinsonian syndromes). Drug-induced parkinsonism was related to 1, 2, 3, 4, 5 and 7 drugs in 62, 30, 9, 1, 2 and 1 patients, respectively. The most frequently offending drugs were: calcium-channel blockers (61 cases), antipsychotic drugs (29 cases), thiethylperazine (18 cases), clebopride (14 cases), and sulpiride (10 cases). When compared with idiopathic Parkinson's disease patients, DIP patients were predominantly female and showed an older age at the onset of parkinsonian signs. Parkinsonian signs only disappeared completely in 41 patients (39.0%). IN CONCLUSION: (1) DIP was a frequent cause of parkinsonism in our Movement Disorder Unit, (2) calcium-channel blockers, and/or orthopramides and substituted benzamides were a frequent cause of DIP in our series, (3) old age and the female gender were frequent among DIP patients, (4) DIP is not always reversible.

Plasma levels of inorganic sulfates in patients with Parkinson's disease.

Some investigators reported pharmacogenetic differences in the metabolism of sulfur-containing drugs and lower plasma sulfate levels in patients with Parkinson's disease (PD) compared with controls. However, other group did not confirm these findings. We studied the plasma levels of sulfate by indirect atomic absorption spectrophotometry in 55 PD patients and 57 age and sex-matched controls. The plasma sulfate levels did not differ significantly between PD patients and control groups (mean +/- SEM 73 +/- 8 and 75 +/- 7 mg/l, respectively). They were not influenced by antiparkinsonian drugs and they did not correlate with age at onset, duration, Hoehn & Yahr staging or activities of daily living subscale of the Unified Parkinson's disease rating scale. There was a low but significant correlation of plasma sulfate levels with motor examination (r = -0.39, p < 0.05) and total score (r = -0.33, p < 0.05) of this scale in the PD group. These data suggest that plasma sulfate levels are apparently unrelated with the risk for PD.