Diabetic coma and Wernicke-Korsakoff syndrome. On the clinical significance of acquired thiamine deficiency

Following consideration of the nosological role of hyperglycemic states in psychiatry the case report of a fifty-five year-old patient is presented suffering from fatty cell degeneration of the liver and a relapsing pancreatitis due to chronic alcoholism. After a long period of abstinence without previously known diabetes mellitus a sudden ketoacidotic coma developed with maximum serum glucose level of 2020 mg%. Having emerged during coma treatment Wernicke's encephalopathy passed into Korsakoff's syndrome the main features of which remained unchanged for more than one year. In this case thiamine deficiency of different pathogenetical origin is discussed: defective exogeneous availability due to malabsorption; depletion of endogeneous thiamine stores due to enlarged requirements for glucose oxidation during coma therapy; antimetabolic effects to thiamine by nitroimidazole-derivatives administered parenterally.     

Magnesium deficiency as a cause of acute intractable seizures

Summary Clinical and experimental investigations have shown that magnesium depletion causes a marked irritability of the nervous system, eventually resulting in epileptic seizures. Although magnesium deficiency as a cause of epilepsy is uncommon, its recognition and correction may prove life-saving. Two case reports are presented which emphasize the importance of recognizing hypomagnesaemia in patients with acute intractable seizures.     

Myopathy in thiamine deficiency: analysis of a case

BACKGROUND: Tenderness in the limb muscles has been reported anecdotally in patients with beriberi neuropathy, but clinical effects of thiamine deficiency on skeletal muscle have received little attention. OBJECTIVE: To describe a patient with thiamine deficiency who manifested myopathic symptoms and responded well to thiamine supplementation. PATIENT: A 26-year-old woman with neuropathy and heart failure associated with thiamine deficiency also complained of myalgia and weakness, most troublesome in the proximal portions of the limbs. RESULTS: Serum creatine kinase, myoglobin, and aldolase concentrations were abnormally elevated. Magnetic resonance imaging of lower limb muscles demonstrated areas of high signal intensity in T2-weighted images and showed Gd-DTPA enhancement. A biopsy specimen from the quadriceps muscle showed myopathic changes without neurogenic changes. Abnormalities improved well with thiamine administration. CONCLUSION: Myopathy may occur in patients with thiamine deficiency.     

Short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency in muscle: a new cause for recurrent myoglobinuria and encephalopathy.

We report on a 16-year-old girl with short-chain L-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase deficiency resulting in juvenile-onset recurrent myoglobinuria, hypoketotic hypoglycemic encephalopathy, and hypertrophic/dilatative cardiomyopathy. Urinary organic acids showed traces of 3-hydroxy-dodecanedioic acids and small amounts of suberic, sebacic, and adipic acids. There was a marked decrease in L-3-hydroxyacyl-CoA dehydrogenase activity in muscle with acetoacetyl-CoA as substrate (2.48 mumol/min/gm; normal = 6.90 +/- 1.80 mumol/min/gm of tissue; n = 11), contrasting with normal L-3-hydroxyacyl-CoA dehydrogenase activity with 3-ketooctanoyl-CoA and 3-ketopalmitoyl-CoA as substrates. Short-chain L-3-hydroxyacyl-CoA dehydrogenase activity was normal in fibroblasts, suggesting a tissue-specific defect.     

Dialysis encephalopathy: a possible seizure disorder.

Dialysis encephalopathy is a progressive, fatal condition that occurs in patients receiving hemodialysis. It is characterized by abnormalities in speech, myoclonic jerks, and striking changes on the electroencephalogram. We observed dramatic reversal of the clinical symptoms and electroencephalographic abnormalities in four patients with this syndrome who were treated with diazepam. In this paper we propose that in dialysis encephalopathy, some of the symptoms and the electroencephalographic changes represent a form of seizure disorder.     

Thiamine-deficient encephalopathy in rats: Effects of deficiencies of thiamine and magnesium

Thiamine- and vitamin B-deficient encephalopathy was produced in adult Wistar rats and the effect of magnesium deprivation and/or the administration of guanidine, a magnesium antagonist, was studied. These encephalopathic rats had symmetrical lesions, edema, exudation of fibrin, spongy changes, petechial hemorrhages, neuronal degeneration and gliosis in the pontine tegmentum, mainly the lateral and medial vestibular nuclear areas. Mild pathological changes were seen in the purely thiamine- or vitamin B-deficient rats, whereas severe pathological changes occurred in thiamine- or vitamin B-deficient rats combined with magnesium deprivation and/or guanidine administration. However, magnesium-deficient diets or guanidine administration did not produce pathologic changes in rats. These findings suggest that thiamine deficiency is an essential factor in the development of these pathological changes in the brainstem, and that magnesium and guanidine, an antagonist of magnesium, play important roles in the development of these disorders.     

Sheep consumption: a possible source of spongiform encephalopathy in humans

A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.     

Carbamyl phosphate synthetase 1 deficiency: a destructive encephalopathy

Carbamyl phosphate synthetase I is a urea cycle enzyme. Severe deficiency of carbamyl phosphate synthetase I presents in the neonatal period as hyperammonemic encephalopathy with altered consciousness and occasional seizures after feeding begins. Episodes of altered consciousness with or without seizures and focal neurologic deficits are seen later with patients of partial carbamyl phosphate synthetase I deficiency. Fatal cerebral edema with brain herniation may develop on occasion. Three patients presenting with carbamyl phosphate synthetase I deficiency are reported with neuroimaging and pathologic findings illustrating the destructive encephalopathy with acute cerebral edema, followed by diffuse cerebral atrophy and occasional cystic encephalomalacia. The deterioration in carbamyl phosphate synthetase I deficiency occurs during the hyperammonemic crises. This deficiency may be difficult to treat despite the current advances in treatment strategies, especially in neonatal-onset patients with low carbamyl phosphate synthetase I activity.     

Brain mitochondrial metabolism in experimental thiamine deficiency

Thiamine deficiency causes Wernicke's encephalopathy, although the precise mechanism is unknown. We used a low-thiamine diet in conjunction with a thiamine analog, pyrithiamine, as a model of severe thiamine deficiency in rats. We investigated the function of intact, coupled mitochondria isolated from both brain and liver. State 4 respiration did not change in the thiamine-deficient animals. Brain state 3 rates fell in thiamine-deficient animals when pyruvate/malate, alpha-ketoglutarate, or glutamate were used as substrate. Liver state 3 rates were depressed only when pyruvate/malate was substrate. Activities of brain and liver pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex were depressed in the thiamine-deficient group. We conclude that the mitochondrial abnormalities resulting from thiamine deficiency are secondary to depression of thiamine-mediated enzyme activity, rather than from a putative role of thiamine in chemiosmotic coupling, and that the resulting abnormalities in ATP synthesis and perhaps in glutamate catabolism result in the irreversible neurologic defect seen in this disease.     

A case of Wernicke-Korsakoff syndrome with dramatic improvement in consciousness immediately after intravenous infusion of thiamine]

A 68-year-old man was hospitalized on March 4, 1998 for disturbances in consciousness. In 1995, he had received proximal subtotal gastrectomy and reconstructive surgery of the jejunal interposition for gastric cancer. Thereafter he had been taking enough food without the habit of taking liquor. In October 1997, his short term memory was becoming gradually worse. On February 12, 1998, he suffered from numbness in the feet, and then dysphagia, unsteady gait, and diplopia developed gradually. On February 26, brain MRI showed no abnormalities. On March 3, he had a fever of 38.5 degrees C and his consciousness became unclear. Neurological examination revealed semi-coma, total ophthalmoplegia, and absence of doll's eye movement. Deep tendon reflexes were absent. The serum thiamine level was 9 ng/ml (normal range: 20-50). Brain MRI demonstrated symmetrical high intensity lesions in the periaqueductal area of the midbrain, dorsomedial nuclei of bilateral thalami, and vestibular nuclei. About 30 seconds after intravenous infusion of thiamine, his consciousness improved dramatically, but returned to semi-coma after about two minutes. Wernicke-Korsakoff syndrome usually occurs acutely. In the present case, however, the disease showed slow onset, chronic progression, and then rapid worsening after fever. Reconstructive surgery of the jejunal interposition might have caused the slow onset of Wernicke-Korsakoff syndrome, and fever might have facilitated the rapid progression of the disease. An immediate high concentration of thiamine modifies the kinetics of acetylcholine receptor ion channels, thereby maintaining wakefulness, and the level of consciousness may change dramatically.     

The medial vestibular nuclei,a vulnerable target in thiamine deficiency

Journal of Neurology - Bilateral medial vestibular nuclei (MVN) is a common target in thiamine depletion and results in acute vestibular failure. Involvement of the MVN was present in 27 out of 38...     

Cerebral toxocariasis: a possible cause of epileptic seizure in children

Introduction Toxocariasis is a worldwide human helminthiasis, which is mostly asymptomatic and caused by toxocara canis, a roundworm in dogs. These can cause visceral larva migrans syndrome in humans who ingest contaminated soil. CNS manifestation with a focal mass lesion is very rare, seizures often being the first symptom.Case report We describe an 11-year-old girl presenting with a generalized epileptic seizure and eosinophilia in blood. Under antibiotic therapy under the assumption of toxoplasmosis the lesion did not decrease and surgical resection was considered. We used computer-assisted surgery (CAS) for careful tissue resection. Postoperatively the diagnosis of toxocariasis was confirmed and albendozole medication was administered for 7 days. The patient developed well without neurological deficits or seizures.Conclusion We conclude that although neurological involvement is rare in toxocariasis, a cerebral infection in a child with epileptic seizures and eosinophilia should be considered.     

Metabolic and histological reversibility of thiamine deficiency

The rapid improvement in the clinical manifestations of thiamine deficiency with thiamine supplementation is well known. To study this process in more detail, we rendered rats thiamine deficient either by dietary deprivation alone (DD) or, in addition, by daily pyrithiamine administration (DD + PT). We observed the cerebral metabolic and histological responses of these rats after 1 or 7 days of thiamine supplementation both prior to and at the onset of clinical sequelae. The cerebral metabolic response to thiamine deficiency and replenishment was determined with the [14C]deoxyglucose technique for measurement of local cerebral glucose utilization (LCGU). Our results indicate that thiamine replenishment reverses the LCGU changes resulting from thiamine deprivation of short duration. However, prolonged thiamine deprivation may result in LCGU changes that are not completely reversible by thiamine replenishment, before the appearance of the clinical or histological consequences of thiamine deficiency.     

Susceptibility of the cerebellum to thiamine deficiency

Thiamine or vitamin B(1), an essential nutrient absorbed from the diet, is involved in vital brain metabolic and cellular functions, including carbohydrate metabolism and neurotransmitter production. Diencephalic regions and, in particular, the cerebellum demonstrate lesions in cases of prolonged thiamine deficiency, such as that observed in alcohol-dependent individuals or in patients with cancer or AIDS. The purpose of this review is to demonstrate recent evidence of cerebellar dysfunction resulting from thiamine deficiency and to assemble theories as to why the cerebellum may be sensitive to this type of insult. A brief outline on cerebellar structure and function, as well as a short discussion on thiamine and thiamine deficiency are provided before detailing the conditions and mechanisms underlying thiamine deficiency-induced cerebellar dysfunction. Although much is known regarding cell loss from a lack of thiamine, further work is still required to identify the sequelae of events leading to the susceptibility of the cerebellum to injury stemming from a thiamine deficient diet or impaired thiamine utilization.