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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes treated with riboflavin and nicotinamide for 18 months, during which time previously frequent encephalopathic spells ceased. To confirm clinical benefit, we withdrew treatment and monitored response with muscle 31P magnetic resonance spectroscopy (MRS) and sural nerve conduction studies. Of three prospectively chosen MRS variables, two changed coincidentally with clinical end points; phosphocreatine (PCr)/adenosine triphosphate recovery rates fell in parallel with sural nerve sensory amplitudes, and a drop in muscle bioenergetic efficiency (relationship of inorganic phosphate/PCr to the accelerating force of contracting muscle) coincided with development of encephalopathy. Investigations revealed a deficiency of respiratory complex I and mutation of the mitochondrial tRNA(Leu)(UUR). We suggest that a defective cellular energy state in mitochondrial disease may be partially treatable and that changes seen in appropriate muscle spectroscopy studies may parallel improvement in brain and peripheral nerve function.
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PMID:MELAS syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin. 143 26

Clinical and postmortem findings of a case that had combined alcoholic pellagra encephalopathy and Wernicke disease are described. This 51-year-old malnourished and chronic alcoholic man presented with progressive mental deterioration, pellagra dermatitis, hypertonus of the neck and other musculatures, myoclonic jerks with bizarre involuntary movements, in addition to total external ophthalmoplegia and gait disturbance. After administration of multivitamins, including thiamine and nicotinamide, these neurologic abnormalities were dramatically improved in a few days. However, the patient died thereafter because of sepsis associated with pneumonia. Postmortem examination revealed marked abnormalities in CNS, characterized by diffuse atrophy of gray matter and widespread neuronal degeneration and characteristic central chromatolysis in pontine nuclei, dentate nuclei, cranial nerve nuclei in the brain stem, Betz cells of the cerebral cortex, and Clarke's column and anterior horn cells of the spinal cord. There were also atrophy and gliosis of the mammillary bodies, degeneration and vascular proliferation of periaqueductal gray matter, and massive gliosis around the third ventricle. These neuropathological changes were compatible with symptoms of both alcoholic pellagra encephalopathy and Wernicke's disease, but they were also strongly suspected on clinical grounds.
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PMID:Alcoholic pellagra encephalopathy combined with Wernicke disease. 188 55

Two infants who had clinical and radiographic findings consistent with Leigh syndrome were found to have deficiency of complex I (reduced nicotinamide-adenine dinucleotide--coenzyme Q reductase) activity. Significant abnormalities were found on computed tomographic scans and magnetic resonance images of the brain. Lactate and pyruvate concentrations in blood and cerebrospinal fluid were elevated, and muscle biopsy specimens showed abnormal mitochondria. These data indicate that Leigh syndrome, as well as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) may result from complex I deficiency.
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PMID:Complex I (reduced nicotinamide-adenine dinucleotide-coenzyme Q reductase) deficiency in two patients with probable Leigh syndrome. 210 30

Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5'-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial enzymatic activities parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of post-hemorrhagic encephalopathy.
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PMID:Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase. 221 48

Oral ingestion of a new rat poison that antagonizes nicotinamide metabolism, N-3-pyridylmethyl-N'-p-nitrophenyl urea (PNU, Vacor), is known to cause diabetes mellitus. I describe neurologic complications of PNU ingestion in 12 patients 19 to 50 years of age who swallowed between 0.39 and 7.02 g of PNU. One died within a day, and five died of chronic complications 40 to 182 days after taking the poison. Apart from the acute hyperglycemic ketoacidosis, the clinical presentation was variable, but orthostatic hypotension, gastrointestinal hypomotility, peripheral neuropathy, and encephalopathy were typical. The peripheral, autonomic, and central-nervous dysfunction could develop either acutely or other several days. It is possible that nicotinamide, given parenterally within minutes, prevents toxicity, but the cases discussed in this paper indicate that the neurologic deficits may progress despite later nicotinamide administration. Neurologic improvement took many months. Full recovery was uncommon, and the orthostatic, hypotension tended to persist.
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PMID:The neurotoxicity of the rat poison vacor. A clinical study of 12 cases. 624 67

Lesions in the CNS induced by 6-aminonicotinamide (6-AN) presented a spongy state of the gray matter and neuronal chromatolysis. With aging of the experimental animals the lesions extended from the phylogenetically early developed structures to those developed later, i.e., from spinal gray matter, dentate nuclei, and brain stem nuclei through limbic structures and striatum to the cerebral cortex. Changes of the neurons were more prominent with aging. Lesions in the CNS of rats at the age, corresponding to the involutional period in the human, were similar to those of Creutzfeldt-Jakob disease (C-J) disease) in the presenile age. In recent years, the resemblance between C-J disease and pellagra encephalopathy had been noted by several authors, and they resemble the lesions caused by 6-AN, an antimetabolite of nicotinamide used in our experiment. This evidence, therefore, has led to the hypothesis that dysfunction of NAD(H)- or NADP(H)-dependent enzymes in the CNS of the aged, even if not the primary cause, may be one possible pathogenetic factor of C-J disease.
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PMID:Ultrastructure of 6-aminonicotinamide (6-AN)-induced lesions in the central nervous system of rats. II. Alterations of the nervous susceptibility with aging. 644 91

Plasma concentrations of magnesium were low in 32 alcoholics and 19 patients with delirium tremens. Vitamin B 1 was lowered only in delirium tremens. After discharge, 39 patients were in remission and 12 present signs of alcoholic encephalopathy. The development of encephalopathy can be predicted when delirium tremens is associated with a low plasma concentration of magnesium and vitamin B 1 and admission. One can thus conclude that encephalopathy after discharge is not caused in alcoholics by deficiencies in magnesium or vitamine B 1 or both together.
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PMID:Plasma concentrations of magnesium and vitamin B-1 in alcoholism and delirium tremens. Pathogenic and prognostic implications. 730 18

Pathological findings from two patients with clinical symptoms of diffuse encephalopathy who died due to a bronchopneumonia are studied. Postmortem examination of the central nervous system revealed neuronal changes which suggested the diagnosis of pellagroid encephalopathy. The differential diagnosis between several diseases characterized by encephalopathy, alcohol ingestion and malnutrition are discussed (chronic alcoholism, acquired hepatocerebral degeneration, Marchiafava-Bignami's syndrome, Morel's lamilar sclerosis, Wernicke-Korsakoff's syndrome and pellagroid encephalopathy). Alcoholic encephalopathy should be considered a medical emergency, which requires early correction of the basal parameters and prompt administration of thiamin and nicotinamide-nicotinic acid in doses of 500 mg per day i.v. followed by 200-300 mg per day of niacinamide by mouth.
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PMID:[Pellagroid encephalopathy in chronic alcoholism. Clinicopathological study (author's transl)]. 741 37

Alcoholic pellagra-encephalopathy is an underestimated entity, which is characterized by alteration in the level and content of consciousness, marked oppositional hypertonus and myoclonus. This entity should be included in the differential diagnosis of encephalopathy in ethanol abusers. The spontaneous course is potentially lethal. Therapy consists of substitution of nicotinic acid in the form of nicotinamide. It is emphasized that any chronic ethanol abuser with neurological symptoms should receive substitution of all B-group vitamins including nicotinamide.
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PMID:[Alcoholic pellagra encephalopathy: an underestimated treatable entity]. 820 69

The pathophysiological significance of the mitochondrial microangiopathy in MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome was evaluated in an autopsy study of a nearly 13-year-old girl who had suffered from multiple infarctlike lesions in the brain, a mitochondrial myopathy-cardiomyopathy, and a generalized mitochondrial microangiopathy. Cytochemically, defects of cytochrome c oxidase (complex IV) were visualized by light and electron microscopy in the skeletal and heart muscle and in the altered vessels, as well as in single bile duct cells, with the activity of the hepatocytes being diffusely reduced, whereas in the brain, the cytochemical activity was only slightly diminished. Biochemical studies revealed a 50% reduction of both NADH (the reduced from of nicotinamide-adenine dinucleotide) dehydrogenase (complex I) and complex IV in the skeletal muscle. In the brain, complex I was diminished to 20%, whereas complex IV was only slightly below the low-normal range. Immunohistochemical studies with the use of subunit-specific antiserum samples against cytochrome c oxidase showed a varying protein profile, with loss of both mitochondrially and nuclearly derived subunits being most pronounced in the heart muscle and lesser in the skeletal muscle. In the brain, liver, bile ducts, and especially the vessels, no loss of enzyme protein content was observed. The results illustrate heterogeneous tissue expression of respiratory chain defects in MELAS syndrome and indicate that vascular cytochrome c oxidase deficiency may be involved in the cerebral manifestation of the disease, whereas in other organs like the heart, a similar pathogenetic importance of the microangiopathy cannot be verified.
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PMID:Generalized mitochondrial microangiopathy and vascular cytochrome c oxidase deficiency. Occurrence in a case of MELAS syndrome with mitochondrial cardiomyopathy-myopathy and combined complex I/IV deficiency. 838 Dec 71


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