Dialysis encephalopathy syndrome

Alfrey AC, LeGendre GR, Kaehny WD. 1976. The dialysis encephalopathy syndrome Possible aluminum intoxication. N Engl J Med 294 184-188. 

In the past several clinical patterns have been described. The most important recognized clinical patterns or types of Al toxicity include two types of encephalopathy. Firstly, the classical dialysis dementia sometimes referred to as dialysis encephalopathy syndrome (DES) or dementia dialytica [24, 28, 37, 42, 70-74] and secondly, the acute or subacute Al encephalopathy [41]. There are also two types of bone disease - either osteomalacia with bone fractures and proximal myopathy or aplastic bone disease [41, 75, 76]. There is quite some confusion in the definitions of Al toxicity in the literature. Because there seems to be an obligatory lag phase of at least several days to weeks for symptoms to occur, acute Al encephalopathy, defined as a direct result of a single overdose, probably does not exist. Because of the long lag phase of several months to years necessary to develop the chronic dialysis encephalopathy and also because acute Al encephalopathy has an abrupt, sudden onset of symptoms one can understand why the term acute is used instead of the more descriptive subacute . The descriptions dialysis dementia [37, 42, 46, 73, 74] and dialysis encephalopathy [33-36, 38, 40, 41, 78] are also unfortunate because true dementia is rare in Al encephalopathy [73] and non-dialyzed patients can also develop these symptoms [78]. There are also many dialysis-related encephalopathy syndromes unrelated to Al. As an example,... 

Ward MK, Pierides AM, Fawcett P. Dialysis encephalopathy syndrome. Proc EDTA 1976 13 348-54. 

Alfrey AC, LeGendre GR, Kaehny WD The dialysis encephalopathy syndrome possible aluminum intoxication. N Engl] Med 294 184-188, 1976 American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000... 

Etheridge WB, O Neill WM The dialysis encephalopathy syndrome without dialysis. Clin Nephrol 10 250-252, 1978... 

Prolonged, elevated Al accumulation in renally impaired humans can produce the dialysis encephalopathy syndrome (DES) (Alfrey et al 1976). Al was significantly elevated in bulk brain ( 10-fold), neurons, and bone ( 85-fold) in DES (Alfrey etal. 1980, Reusche 1997). Although generally well recognized and avoided, DES still... 

DES Dialysis encephalopathy syndrome Descemet s membrane a specific layer of the optic cornea in which deposits of copper are visible in patients with Wilson s disease desquamation separation of the cuticle or skin in scales... 

Alfrey AC, LeGendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome. Possible aluminium intoxication. N Engl J Med 294 184-188 Antonny B, Chabre M (1992) Characterization of the aluminum and beryllium fluoride species which activate transducin. J Biol Chem 267 6710-6718 Antonny B, Sukumar M, Bigay J, Chabre M, Higashijima T (1993) The mechanism of aluminum-independent G-protein activation by fluoride and magnesium. J Biol Chem 268 2393-2402... 

Parkinson, I.S., Ward, M.K., and Kerr, D.N.S. (1981) Dialysis encephalopathy, bone disease and anaemia the aluminum intoxication syndrome during regular haemodialysis. /. Clin. Pathol., 34, 1285-1294. 

In summary, dialysis dementia probably represents an end point in a disease of multiple etiology. There are at least three subgroups and in two of them the etiology of dialysis encephalopathy must be regarded as unknown. The possible role of aluminum, or other trace element abnormalities, is unclear. At this time, there is no known satisfactory treatment for patients with dialysis encephalopathy. Most patients reported in the literature thus far have not survived, usually dying within 18 months of the time of diagnosis. The syndrome is not alleviated by increased... 

It remains remarkable that, after the discovery of chronic Al encephalopathy and numerous reports of patients suffering from this syndrome, fourteen years passed before the first publication on acute Al neurotoxicity appeared [62], Acute Al encephalopathy is a devastating, often fatal disease that is the result of iatrogenic exposure to Al. Unfortunately, in spite of efforts to avoid Al exposure as much as possible, recently new sources of serious exposure have been added to the growing list of sources of Al exposure. In contrast to a fascinating history and abundant literature, many uncertainties about Al toxicity still exist. Clinical data in humans on acute Al neurotoxicity are very limited and we will, therefore, compare our experience in one of the two documented outbreaks in dialysis centers, with that of the literature. 

A unique set of circumstances was responsible for symptoms resembling hard water syndrome [64] followed by an epidemic of acute Al encephalopathy in a dialysis unit (Diatel) on the island of Curasao. A tragic coincidence is that the intoxication happened about two months before the planned installation of a water treatment system with deionization and reverse osmosis (RO). Traditionally, municipal water had been used for more than two decades without extended purification for the production of dialysate. The pure... 

Uremic encephalopathy occurs as a result of the effects of uremia on the central nervous system and is associated with symptoms including alterations in consciousness, thinking, memory, speech, psychomotor behavior, and emotion. Sensory and motor function may be altered, particularly affecting leg nerves, resulting in leg cramps and restless leg syndrome. Uremic encephalopathy is less common because of earlier initiation of dialysis in patients with Stage 5 CKD. 

As patients live longer with dialysis treatment, they begin to develop yet another set of problems related to dialysis itself, and to the chronic accumulation of endogenous compounds (p2-microglobulin) and exogenous toxins (aluminum). P2-Microglobulin causes dialysis amyloidosis with the carpal tunnel syndrome and destructive arthropathy. Aluminum causes anemia, osteomalacia or adynamic bone disease, and encephalopathy. 

The evidence available thus far indicates that aluminum is elevated in the brain (cortical gray matter) of patients with dialysis dementia. However, the actual contribution of aluminum to the encephalopathy remains unclear. Aluminum content has been reported to be elevated in the brains of patients with other disorders, including senile dementia and Alzheimer s syndrome, and might actually be a nonspecific finding associated with dementia. Aluminum is also elevated in the brains of patients who have other disorders associated with altered blood-brain barrier. Such disorders include renal failure, hepatic encephalopathy and metastatic cancer. Other evidence suggests that brain aluminum content may also increase as a function of the aging process.Blood-brain barrier abnormalities can result in increased brain aluminum content (Banks Kastin, 1983). 

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