Encephalopathy clinical forms

The expression hepatic encephalopathy (HE) is a collective term covering five clinical forms of disease (H.O. Conn, 1989) (7.) Reyc s syndrome, (2.) enzyme deficiency of the urea cycle, (i.) pseudoportosystemic encephalopathy, (4.) fulminant liver failure, and (J.) portosystemic encephalopathy. It is not known whether the pathogenic mechanisms of these various clinical forms are identical, (s. tab. 15.3)... 

Portosystemic encephalopathy (PSE) develops in chronic liver diseases and/or in the wake of portosystemic circulation. Liver cirrhosis with its hepatofugal collateral circulatory pathway is thus the focus of interest in this clinical form of disease. The term PSE is identical to exogenous liver coma or liver cell failure coma . PSE can be further subdivided according to its symptomatology and depending on its form and degree of severity. There are three forms of portosystemic encephalopathy (1.) subclinical (or latent) PSE, (2.) acute or acute recurrent (episodic) PSE, and (i.) chronic recurrent or chronic persistent PSE. 

Beri-beri or clinically manifest thiamin deficiency exists in several subforms infantile beri-beri and adult beri-beri. Infantile beri-beri occurs in exclusively breastfed infants of thiamin-deficient mothers. Adults can develop different forms of the disease, depending on their constitution, environmental conditions, the relative contribution of other nutrients to the diet as well as the duration and severity of deficiency. First of all, there is a so called dry or atrophic (paralytic or nervous) form, including peripheral degenerative polyneuropathy, muscle weakness and paralysis. Second, a wet or exudative (cardiac) form exists. In this form, typical symptoms are lung and peripheral oedema as well as ascites. Finally, there is a cerebral form, that can occur as Wernicke encephalopathy or Korsakoff psychosis. Tli is latter form mostly affects chronic alcoholics with severe thiamin deficiency. 

One of the most confusing features of Al encephalopathy is the lag phase between exposure and clinical symptoms and the subsequent rapid course of the disease. The delay can be months to years in the classical form and several weeks in the acute form. Because patients are generally symptom-free or demonstrate minor symptoms like microcytic anemia, physicians are unaware of the exposure until the development of severe symptoms. Until recently it was not known that a relatively short dialysis related exposure time to Al can be fatal. 

Despite several decades of clinical experience and animal study, the pathophysiology of brain encephalopathy is far from understood. One of the main reasons for the complexity of the research on Al is the difficult interaction with molecules found in biological systems. In most natural systems, a small fraction of Al is found as the simple Al3+ aquo ion. Thus Al absorption, excretion, tissue retention, and deposition will all depend on the properties of the Al3+ complexes formed with biological ligands. Unfortunately, the search for an accurate description of Al complexation equilibria and kinetics has been consistently frustrated by the tendency of both free Al3+ ion and simple Al complexes to hydrolyze at or below neutral pH. 

The acute or acute recurrent form can be equated with the manifestation of portosystemic encephalopathy in chronic liver disease. It is also known as acute episodic form . Discrete psychometric disorders usually precede the manifest picture as a latent stage. Manifestation includes stages I-IV and hence covers a wide spectrum of clinical, neurological and psychopathological symptoms. Once the liver function is stabilized and the trigger factors are eliminated, all the symptoms of this form are as a rule reversible. 

Clinically, there are three different courses of disease following the onset of jaundice .) fulminant or hyperacute liver failure (= occurrence of hepatic encephalopathy in the 1 week), (2.) acute liver failure (= occurrence of hepatic encephalopathy between the and 4 week), and (5.) subacute liver failure (= occurrence of hepatic encephalopathy between the 5 and 8 week). Surprisingly, however, it could be shown that 30-40% of the hyperacute forms survived in spite of the development of hepatic coma and cerebral oedema. As opposed to this, the subacute forms displayed a survival rate of only 10-20%, despite a lower frequency of cerebral oedema and better liver function, (s. tab. 20.1)... 

HE can present in one of three forms acute, chronic, and sub-clinical. Acute HE is defined as a distinct event of altered sensorium lasting <4 weeks, followed by complete recovery to the baseline mental status. Chronic encephalopathy is defined as cognitive or neuropsychiatric abnormalities that persist for at least 4 weeks. During this time, the severity of the abnormalities fluctuates, but no episodes of normal mentation are noted. Subclinical encephalopathy refers to subtle alterations in neuropsychiatric function that are not clinically apparent without special testing. ... 

In the past, some concern has been voiced that long-term alumina-bearing implants could lead to elevated concentration of aluminium in the body (Lewandowska-Szumiel and Komender, 1990). Such enhanced aluminium levels are considered to be an aetiological agent in dialysis osteomalacia, encephalopathy and some forms of anaemia (Alfrey, 1984 Parkinson, Ward and Kerr, 1981). However, since to date there are no clinical reports on the upper safety levels of aluminium in human bone the effect of even minute quantities of aluminium released from alumina femoral heads needs further investigation. 

Pyruvate carboxylase deficiency is one of the genetic diseases grouped together under the clinical manifestations of Leigh s disease (subacute necrotizing encephalopathy). In the mild form, the patient presents early in life with delayed development and a mild-to-moderate lactic acidemia. Patients who survive are severely mentally retarded, and there is a loss of cerebral neurons. In the brain, pyruvate carboxylase is present in the astrocytes, which use TCA cycle intermediates to synthesize glutamine. This pathway is essential for neuronal survival. The major cause of the lactic acidemia is that cells dependent on pyruvate carboxylase for an anaplerotic supply of oxaloacetate cannot oxidize pyruvate in the TCA cycle (because of low oxaloacetate levels), and the liver cannot convert pyruvate to glucose (because the pyruvate carboxylase reaction is required for this pathway to occur), so the excess pyruvate is converted to lactate. 

If the patient with kidney failure also has cirrhosis or some other form of hver failure, this additional ammonia load may present a stress that cannot be adequately handled by the diseased liver. The result may be increased blood and central nervous system ammonia levels with development of encephalopathy (Fraser Arieff, 1985). Thus, patients with cirrhosis and end-stage kidney disease are at particular risk for developing encephalopathy since both conditions act synergistically to increase both blood and central nervous system ammonia. It should also be noted that plasma urea and serum creatinine do not always adequately reflect renal function in patients with severe liver disease. Recent studies suggest that many patients who have cirrhosis, ascites, and normal plasma urea and creatinine may in fact have severe renal functional impairment (Gines et al., 1988 Papadakis Arieff, 1987 Takabatake et al., 1988). In such individuals, differentiation of hepatic from uremic encephalopathy on clinical grounds may be difficult. 

At present, the important clinical indication areas for therapy with thiamine are the beriberi of alcoholics and Wernicke s encephalopathy (Korner and Vollm 1976). In both cases, therapy is started with daily doses of at least 50-100 mg (in severe cases up to 200 mg) thiamine administered parenterally. Therapy is then continued with oral doses of 100-300 mg daily. Neuritis accompanying pregnancy responds particularly well to vitamin therapy. In some severe disorders of the intermediate metabolism (e.g., diabetic acidosis, severe hepatic malfunction), the necessary phosphorylation of thiamine in the organism is no longer ensured. Thiamine has, therefore, to be administered directly in its active form, thiamine pyrophosphate (TPP, cocarboxylase). Instances of toxicity of thiamine have been reported, primarily showing effects on the cardiovascular and nervous systems (Un-NA 1972 DiPalma and Ritchie 1977). 

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