Survival and clinical outcome of dogs with ischaemic stroke.

The objectives of the present study were to investigate survival time, possible predictors of survival and clinical outcome in dogs with ischaemic stroke. A retrospective study of dogs with a previous diagnosis of ischaemic stroke diagnosed by magnetic resonance imaging (MRI) was performed. The association between survival and the hypothesised risk factors was examined using univariable exact logistic regression. Survival was examined using Kaplan-Meier and Cox regression. Twenty-two dogs were identified. Five dogs (23%) died within the first 30days of the stroke event. Median survival in 30-day survivors was 505days. Four dogs (18%) were still alive by the end of the study. Right-sided lesions posed a significantly increased risk of mortality with a median survival time in dogs with right-sided lesions of 24days vs. 602days in dogs with left sided lesions (P=0.006). Clinical outcome was considered excellent in seven of 17 (41%) 30-day survivors. Another seven 30-day survivors experienced new acute neurological signs within 6-17months of the initial stroke event; in two of those cases a new ischaemic stroke was confirmed by MRI. In conclusion, dogs with ischaemic stroke have a fair to good prognosis in terms of survival and clinical outcome. However, owners should be informed of the risk of acute death within 30days and of the possibility of new neurological events in survivors. Mortality was increased in dogs with right-sided lesions in this study.

Endocrine function in 97 patients with myotonic dystrophy type 1.

The aim of this study was to investigate the endocrine function and its association to number of CTG repeats in patients with myotonic dystrophy type 1 (DM1). Concentration of various hormones and metabolites in venous blood was used to assess the endocrine function in 97 patients with DM1. Correlation with CTG(n) expansion size was investigated with the Pearson correlation test. Eighteen percent of the DM1 patients had hyperparathyroidism with increased PTH compared with 0.5% in the background population. Of these, 16% had normocalcemia and 2% had hypercalcemia. An additional 3% had hypercalcemia without elevation of PTH; 7% had abnormal TSH values (2% subnormal and 5% elevated TSH levels); 5% of the patients had type 2 diabetes mellitus; 17% of the male DM1 patients had increased LH and low levels of plasma testosterone indicating absolute androgen insufficiency. Another 21% had increased LH, but normal testosterone levels, indicating relative insufficiency. Numbers of CTG repeats correlated directly with plasma PTH, phosphate, LH, and tended to correlate with plasma testosterone for males. This is the largest study of endocrine dysfunction in a cohort of Caucasian patients with DM1. We found that patients with DM1 have an increased risk of abnormal endocrine function, particularly calcium metabolism disorders. However, the endocrine dysfunction appears not to be of clinical significance in all of the cases. Finally, we found correlations between CTG(n) expansion size and plasma PTH, phosphate, and testosterone, and neck flexion strength.

Axonal recovery after severe traumatic brain injury demonstrated in vivo by 1H MR spectroscopy.

Proton magnetic resonance spectroscopy (MRS) suggested almost complete axonal recovery 21 months after trauma in a patient with severe diffuse axonal injury. MRS while the patient was comatose showed evidence of severe diffuse axonal injury in occipitoparietal white matter, but occipital grey matter was relatively spared. At 21 months N-acetylaspartate was normal. At 33 months examination showed a Functional Independence Measure of 83 and a Rancho Los Amigos Scale of Cognitive Function of 7-8, a remarkable improvement considering all the initial findings, except those of MRS.

Neurotoxic interactions of industrially used ketones.

Occupationally workers are most often exposed to a mixture of solvents. Exposure limits are, however, usually set separately for single solvents. So we reviewed the present knowledge about possible neurotoxic interactions of the industrially most used ketones acetone (ACE), methyl ethyl ketone (MEK) and methyl isobutyl ketone (MIBK) with solvents in general. A literature search from the last 25 years (1974-1998) revealed 54 original publications describing neurotoxic monitoring after combined exposure (experimental and occupational) involving the mentioned ketones. Animal exposure was described in 27 reports, exposure involving human volunteers in 12 reports, and occupational surveys constituted 15 reports. Of the 54 papers, 25 dealt with potentiation by ACE, MEK or MIBK of n-hexane or 2,5-hexanedione (2,5-HD) induced neurotoxicity. Possible synergistic interactions of the ketones were reported in 12 of the 29 remaining works. Only two studies reported neurotoxic potentiation after acute short-term combined exposure to human volunteers. Possible neurotoxic potentiation by the ketones after occupational mixed exposure without the involvement of n-hexane or 2,5-HD, were reported in 8 papers. Some studies reported a different outcome of metabolic interactions based on animal or volunteer exposure, compared to more long-term occupational exposure. We conclude that the widespread use of the rule of additivity often underestimates the effect when dealing with combined exposure to industrially used ketones. We also conclude that the results of combined exposure obtained in animals or human volunteers cannot necessarily be extrapolated to occupational situations. More research is needed in particular concerning the most frequently occurring mixtures comprising ketones and aromatic solvents such as acetone (ACE) and styrene as well as methyl isobutyl ketone (MIBK) and toluene.

LDL receptor mutations and ApoB mutations are not risk factors for ischemic cerebrovascular disease of the young, but lipids and lipoproteins are.

BACKGROUND: The genetic background for ischemic cerebrovascular disease of the young and the role of lipids and lipoproteins as risk factors are not clear. METHODS: We determined five LDL receptor mutations (Trp23Stop, Trp66Gly, Trp556Ser, 313+1G --> A, 1846-1G --> A) and three apolipoprotein B mutations (Arg3500Gln, Arg3500Trp, Arg3531Cys), and other risk factors for ischemic cerebrovascular disease in 80 patients (36 women, 44 men) with onset of disease before the age of 50 years compared with 3366 individuals from a general population sample within the same age range. RESULTS: None of the patients were carriers of mutations in the LDL receptor (Trp23Stop, Trp66Gly, Trp556Ser, 313+1G --> A, 1846 - 1G --> A) or the apolipoprotein B gene (Arg3500Gln, Arg3500Trp, Arg3531Cys) associated with hypercholesterolemia. However, on univariate analysis as well as on logistic regression analysis allowing for age and gender, plasma cholesterol (OR 1.4; P < 0.0005), HDL-cholesterol (OR 0.4; P < 0.005), diabetes (OR 5.8; P < 0.0001), and hypertension (OR 3.9; P < 0.001) were significant predictors of ischemic cerebrovascular disease. CONCLUSIONS: The five most common LDL receptor mutations in Danish patients with familial hypercholesterolemia and three mutations in the apolipoprotein B gene did not predispose to ischemic cerebrovascular disease of the young. However, cholesterol and HDL-cholesterol are important risk factors for ischemic cerebrovascular disease of the young in the present study. The elevation in cholesterol could in some patients be due to rare LDL receptor mutations not tested for, and could in other patients be multifactorial in origin.

[Cerebral dysfunction occurring after years of latency]. / Cerebral dysfunktion optraedende efter års latenstid.

A number of basically very different factors may affect the central nervous system and result in progressive loss of mental or physical functions immediately or after a latent period of decades, possibly due to the initial factor being combined with an additive effect of aging. Intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of the basal ganglia. Various vira e.g. poliovirus and retrovirus may give rise to acute or late effects after several years. The Concentration Camp Syndrome may lead to a dementing illness with a latency of 10-30 years. Signs of progressive degenerative CNS disease should give rise to considerations of possible provoking factors earlier in the patient's life history.

A new mitochondrial tRNA(Met) gene mutation in a patient with dystrophic muscle and exercise intolerance.

A 30-year-old woman with a novel heteroplasmic U4409C mtDNA mutation in the tRNA(Met) gene presented with growth retardation, muscle weakness, severe exercise intolerance, and lactic acidosis. Muscle biopsy showed unusually severe dystrophic features. The mutation was not present in maternal relatives or 25 healthy subjects. Single-fiber PCR-RFLP analysis of mtDNA showed higher proportion of the mutation in COX-negative than in COX-positive muscle fibers.

Neurological complications to vaccination against Japanese encephalitis.

Japanese encephalitis (JE) vaccine has been used for childhood immunization programmes in Asia since the 1960s. Also, travellers from other parts of the world have been vaccinated before travelling to Asian countries. Some JE vaccines are produced from infected mouse brains and contain small amounts of myelin basic protein. Neurological side effects in larger vaccine trials in Asia have been reported in 1-2.3 per million vaccinees. Statens Serum Institut is the only distributor of JE vaccine in Denmark, delivering 384 000 doses from 1983-96. In 1996, evaluation of initial symptoms and findings in 10 adult travellers from Denmark, who developed moderate-severe neurological symptoms within a few weeks of JE vaccination, was performed as well as follow-up magnetic resonance imaging (MRI) and clinical neurological examination. Three patients initially had symptoms varying from severe encephalitis-like illness to paraesthesia, double vision or parkinsonian gait disturbance. MRI showed severe atrophy of the corpus callosum with altered signal intensity indicating gliosis in one patient, another patient had several hyperintense spots located periventricularly in the white matter, while a third patient had spots with increased signals in the pons, the right substantia nigra and the occipital region. Acute disseminated encephalomyelitis (ADEM) is a possible explanation for these MRI changes, although multiple sclerosis is an alternative diagnosis in one or two of the patients. Another three patients had long-lasting headache, concentration difficulty or intellectual reduction. One man had afebrile convulsions, another gait instability and depression and one parkinsonism. A woman developed myelitis. If these findings are due to JE vaccination the frequency of neurological reactions to the vaccine is considerably higher than previously reported and in the future any minor neurological complaints occurring shortly after vaccination should lead to neurological examination and acute MRI scan should be considered. Copyright 1998 Lippincott Williams & Wilkins

Effect on the content of n-acetylaspartate, total creatine, choline containing compounds, and lactate in the hippocampus of rats exposed to aromatic white spirit for three weeks measured by NMR spectroscopy.

Several epidemiological studies of workers occupationally exposed to white spirit show that neuropsychiatric disorders are a frequent cause of early disability pension in this population compared with non-exposed controls. In the rat, we have demonstrated that exposure to different kinds of white spirit induces changes in neurotransmitter concentrations, indices of oxidative stress, and electrophysiological parameters. Others have confirmed that acute behavioural effects can be induced by short-term high-level exposure. With NMR spectroscopy technique it is possible to study neurochemical parameters in vivo, and to examine the same subjects repeatedly over time. NMR spectroscopy was used to study the effects of organic solvents in rats. Rats were exposed to 0, 400 ppm, or 800 ppm of aromatic white spirit 6 hr/day, 7 days/week for 3 weeks. During the first week, the rats showed signs of irritation of mucous membranes, and appeared to be sedated. Both types of effect gradually diminished during the second week. The rats were examined by single volume of interest (VOI) NMR spectroscopy. N-acetylaspartate, creatinine and phosphocreatinine, and choline containing compounds were measured in the hippocampus and surrounding regions. The concentration of N-acetylaspartate for the three groups was found to be in the range of 8.2-8.5 mM with a standard deviation of 0.6-0.9. There was no difference between the three groups. In a previous study no change in the number of astrocytes in hippocampus was found following exposure to white spirit for six months. Since N-acetylaspartate is thought to be a marker for neurons, the results of these two studies indicate that white spirit does not produce a marked neuronal loss. However, it was not possible to show effect of trimethyltin. In this study trimethyltin was used as a "positive control'. The NMR technique can be applied to the rat, and it is possible to obtain reasonable signal-to-noise ratios.

Neuronal loss in hippocampus in rats exposed to toluene.

Both clinical and epidemiological studies of the effects of exposure to toluene have shown that long-term exposure may result in chronic toxic encephalopathy, where one of the major symptoms is memory deficits. We have attempted to identify the structural basis of the toxic effects of toluene in the hippocampus, a region of the brain known to be involved in learning and memory processes and well suited for stereological analysis. Rats were exposed to 1500 ppm of toluene, six hours per day, five days per week for six months. This was followed by a four-month-period without exposure prior to sacrifice. The total number of neurons in each of the five subdivisions of hippocampus of six exposed and six control rats was estimated with the optical fractionator. A statistically significant neuron loss of 16% was found in regio inferior (CA3 and CA2) of the exposed rats.

Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy.

INTRODUCTION: The effect of antiepileptic drugs (AED) on cognitive function was studied in 87 patients with epilepsy. MATERIAL AND METHODS: Group A: (n = 52) started AED treatment (carbamazepine, oxcarbazepine, sodium-valproate, phenobarbital or phenytoin). Group B: (n = 27) had AED monotherapy withdrawn (carbamazepine or sodium-valproate). Group C: (n = 8) was switched from phenytoin to carbamazepine monotherapy. The patients were tested before and 4 months after change of the treatment. RESULTS: In group A the test performances were in general unchanged. Patients who had their drug treatment withdrawn (group B) and the patients who were switched from phenytoin to carbamazepine (group C) improved in single tests. The predominant changes in performance seem to be due to practice effect. CONCLUSION: Cognitive functions are only minimally influenced by AEDs after short-term treatment whereas there is a slight improvement after discontinuation of long-term administration of carbamazepine and valproate. A lack of practice effect might be the first indicator of a negative effect of AED on cognitive function.

Long-term follow-up of cerebral infarction patients with proton magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: With proton magnetic resonance spectroscopy it is possible to measure the content of various brain metabolites in vivo, including N-acetylaspartate (which may be used as a neuronal marker), creatine, choline, and lactate. The content of these brain metabolites was measured serially from the acute stage to the chronic stage of infarction. Regional cerebral blood flow was also measured within the affected areas. These factors were compared with the clinical outcome. METHODS: Six patients with ischemic stroke were examined serially from the acute stage (< or = 2 days) to the chronic stage (> 6 months) with proton magnetic resonance spectroscopy. Cerebral blood flow was measured with single-photon emission-computed tomography with 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as flow tracer. RESULTS: Lactate was found in all patients in the acute stage of stroke. Lactate was also found in the 3 largest lesions in the chronic stage; in 2 of these patients lactate was not found in the subacute stage. Reduced levels of N-acetylaspartate were found in 5 patients; in the sixth patient with a small lesion no reduction was found. In all lesions reduced blood flow was found in the acute and chronic stage, whereas hyperemia was found in 4 patients in the subacute stage. CONCLUSIONS: In this preliminary study no clear correlation was found between the level of N-acetylaspartate or lactate in the acute stage of stroke and the clinical outcome; however, there does appear to be some connection between the reduction of cerebral blood flow and the spectroscopic findings in the chronic stage and to some extent the clinical outcome. Studies of larger clinical groups will be necessary to further elucidate the prognostic potential of proton magnetic resonance spectroscopy in human stroke.

[Magnetic resonance spectroscopy of acute cerebral infarctions]. / Magnetisk resonansspektroskopi af akutte cerebrale infarkter.

Eight patients with brain infarction were examined serially in the acute phase and one week and two to four weeks after stroke with water-suppressed proton magnetic resonance spectroscopy. Ten healthy volunteers served as controls. The time courses of N-acetylaspartate (NAA), total creatine (Cr), choline containing compounds (Cho), lactate content, and regional cerebral blood flow (rCBF) measured by SPECT were studied. A high lactate level was found in the acute phase. The lactate content decreased to barely detectable levels during the following two to four weeks, while rCBF increased during this period. The content of NAA in infarcted tissue was significantly reduced (p < 0.01) compared to healthy controls, Cr was also reduced (p < 0.02), whereas Cho content did not change. The inverse relationship between lactate level and cerebral blood flow suggests that lactate plays no substantial role in the vasodilatation underlying the hyperaemia that follows reperfusion. The amount of lactate present in the acute phase reflects the severity of ischaemia in the affected region. The content of NAA may be used as a neuronal marker, and thus perhaps as a marker of the effect of future treatment procedures.

Thrombolytic therapy in acute ischemic stroke. A Danish pilot study.

BACKGROUND AND PURPOSE: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow. METHODS: Twenty-three patients with acute ischemic stroke were treated with 100 mg recombinant tissue plasminogen activator infused intravenously over 1 hour. Thrombolytic therapy was initiated 78 to 355 minutes after onset of symptoms. RESULTS: Angiography 16 to 24 hours after treatment in 17 patients showed patient intracranial arteries in 12, partial occlusion of the middle cerebral artery in 3, and total occlusion of the middle cerebral artery in 2. rCBF with 99mTc-hexamethylpropyleneamine oxime intravenously was measured 5 minutes before and within 24 hours after thrombolytic therapy in 12 patients. 10 of the 12 patients showed brain tissue reperfusion and 2, with angiographically documented middle cerebral artery occlusion, showed no reperfusion, thus documenting a relationship between reperfusion measured by regional cerebral blood flow and angiographic patency (P = .015). Three patients died. Patients who were reperfused within 24 hours (documented by repeated regional cerebral blood flow measurements) showed greater clinical improvement on the Scandinavian Stroke Scale the sooner their thrombolytic therapy was started and the more severe their neurological deficits. CONCLUSIONS: Acute cerebral ischemia can be documented by rCBF measurements without delay of thrombolytic therapy, and repeated rCBF measurements can reveal whether cerebral reperfusion has occurred. In our study, early reperfusion was associated with clinical improvement.

Brain autopsy in organic solvent syndrome.

General autopsy findings, brain weight and brain pathology were studied in 98 men and five women who had been exposed occupationally to organic solvents over several years and assessed by the Danish National Board of Industrial Injuries for chronic toxic encephalopathy. The findings were compared with a forensic control material and a hospital control material. As in the general population, the most common causes of death among the exposed workers were heart failure and other vascular diseases. Due to the composition of the material (forensic cases), the number of suicides and violent deaths was high. Atherosclerosis was the most common CNS finding, but in comparison with the two control materials, no increase in the frequency of atherosclerosis or of Alzheimer's disease was found. Brain weights of the exposed workers corresponded closely to brain weights in the control materials, after correction for body height, body weight and age. Chronic alcoholism was correlated with slightly reduced brain weight.

Clinical neurological findings among metal degreasers exposed to chlorinated solvents.

Among industrial solvents in present use trichloroethylene belongs to those which have been the concern of most neurological and occupational investigations since the beginning of this century. Reports on a broad spectrum of neurotoxicity are however mostly based on case-studies and accidental circumstances. The object of this study was to examine clinical neurological manifestations after long-term exposure to degreasing solvents, mainly trichloroethylene. The population was 99 metal degreasers, the design a historical cohort study. The most marked finding was a highly significant dose-response relation between solvent exposure and motor dyscoordination--a finding that was retained after multivariate control of relevant confounders. Vibration thresholds increased by solvent exposure at bivariate level, but the multivariate analysis showed that age was explaining most of the increase. No significant cranial nerve dysfunction was found.

Myelography, CT, and MRI of the spinal canal in patients with myelopathy: a prospective study.

A prospective study including myelography, CT, and MRI was performed on 36 patients with clinical signs of myelopathy. Evoked potentials and spinal fluid examinations were also carried out. Based on our findings, the patients could be classified as suffering from cryptogenic myelopathy (n = 12), multiple sclerosis (n = 6), spinal stenosis (n = 6), or miscellaneous myelopathies (n = 12). The diameter of the spinal cord was normal in the 2 first groups of patients and of same magnitude evaluated by myelography and CT, while MRI constantly gave higher figures. In only four of the patients important new information was added by CT and MRI (syringomyelia, myelitis, lipomatosis) compared with myelography, although a more precise visualization was often provided. Further diagnostic progress in patients with myelopathy of undetermined etiology may be obtained by including supplementary MRI of the brain disclosing multiple sclerosis in several cases.

Effects of six months' white spirit inhalation exposure in adult and old rats.

In two separate experiments in rats the irreversible effects of six months' exposure to white spirit (0, 400 p.p.m., and 800 p.p.m.) were studied. In one experiment the exposure started at the age of three months, in the other the rats were 15 months at the beginning of the exposure. After an exposure-free period of several months neurobehavioural, pathological, and neurochemical examinations were performed. A marked difference in motor activity between young and aged animals was found. A slight effect on kidney function was seen at 800 p.p.m. No macroscopic or histopathological changes related to dosing were found. The concentrations of noradrenaline, dopamine, and 5-hydroxytryptamine in various brain regions and in whole brain were irreversibly changed. In conclusion, the study revealed different changes within the CNS, but failed to demonstrate neurobehavioural white spirit-induced neurotoxicity.