Renal Disease and the Brain



Renal Disease and the Brain


J. Kirk Roberts

Stephan A. Mayer



INTRODUCTION

Renal disease is most commonly associated with neurologic disease when both are related to an underlying condition (e.g., diabetes mellitus, hypertension) that damages both systems. However, renal disease and resultant azotemia (blood urea nitrogen elevation or uremia) can injure both the central nervous system (CNS) and the peripheral nervous system. With the increase in aggressive kidney dialysis and transplantation, the incidence of many neurologic conditions associated with chronic renal failure has declined, but a new constellation of neurologic complications associated with dialysis and transplantation has become more important.


UREMIC ENCEPHALOPATHY

The differential diagnosis of encephalopathy in a patient with renal failure is wide and includes metabolic, infectious, structural, and other causes. Fluid and electrolyte disturbances are common. Drugs that are excreted in the urine may accumulate and dosing must be adjusted.


PATHOBIOLOGY

Uremia itself can cause encephalopathy. The symptoms of uremic encephalopathy are usually more severe in patients with more severe azotemia; they are often evident earlier and more severely in patients with acute as opposed to chronic renal failure. The specific factors that cause encephalopathy are still not identified. The earliest indicator is sensorial clouding, which progresses to delirium, obtundation, and even coma. In addition to cognitive changes, patients are usually weak, uncoordinated, and unsteady. Focal symptoms or signs may wrongly suggest a focal process. Asterixis is a dramatic problem, with jerking movements arising from lapses of posture holding, as of the outstretched hands. Multifocal myoclonus, involuntary twitches occurring randomly throughout the body, may become apparent, usually after stupor or coma has supervened. Tetany may be overt, with spontaneous carpopedal spasm, or latent as manifest by a Trousseau sign (sustained muscle contraction and cupping of the hand, induced by arterial occlusion). Seizures are a late manifestation of uremic encephalopathy. Fluctuation of clinical symptoms and signs from day to day is characteristic.




DIALYSIS DISEQUILIBRIUM SYNDROME

Dialysis disequilibrium syndrome is usually seen with rapid correction of uremia at the start of a dialysis program. It is more common in those with more severe azotemia. Symptoms vary from mild headache, nausea, and muscle cramps to, rarely, delirium, obtundation, and convulsions. The syndrome is usually selflimited, subsiding in hours, but delirium may persist for several days. Although the pathogenesis is controversial, shift of water into brain is probably the cause of syndrome. The rapid reduction in blood osmoles cannot be paralleled as rapidly by a reduction in brain osmoles, resulting in an osmotic gradient between blood and brain, causing movement of water into brain and cerebral edema and encephalopathy. With improvements in dialysis, this syndrome is much less frequent now. Gradual initiation of dialysis may help prevent. Before diagnosing dialysis disequilibrium, other causes of cerebral symptoms should be excluded. If it seems likely, dialysis should be stopped and supportive care provided. Some have suggested hypertonic saline or mannitol for severe cases but this is not routine.


DIALYSIS DEMENTIA

A subacute, progressive, usually fatal encephalopathy rarely occurs in patients who are chronically dialyzed. The first symptom is usually a stammering, hesitancy of speech and at times, speech arrest. The speech disorder is intensified during and immediately after dialysis and at first may be seen only during these periods. As the disorder progresses, speech becomes more dysarthric and aphasic along with personality change, psychosis, myoclonus, seizures, and occasionally focal neurologic abnormalities. Brain imaging and CSF findings are usually unremarkable and, again, are most helpful in excluding other causes of encephalopathy. Increased dialysis
time and renal transplantation do not seem to alter the course of the disease. Aluminum content is consistently elevated in the cerebral gray matter of patients who die from this condition. Municipal water supplies heavily contaminated with aluminum have been linked to the syndrome in epidemiologic studies. The frequency of the disease markedly diminished when aluminum was removed from the water used during dialysis but did not disappear completely. Another possible source is absorption of aluminum from orally administered phosphate-binding agents that are given to uremic patients.


CEREBROVASCULAR DISEASE

Stroke is prevalent in patients with renal failure, mostly because of shared risk factors. However, renal failure may additionally promote atherogenesis through several mechanisms. Hypotension during dialysis may result in watershed infarction. Renal failure is associated with platelet dysfunction, and anticoagulants used during hemodialysis may contribute to intracerebral hemorrhage or subdural hematoma. Chronic subdural hematoma may present with an encephalopathic picture without focal motor or sensory symptoms and signs. Autosomal dominant polycystic kidney disease is associated with an increased risk of saccular aneurysm and subarachnoid hemorrhage (SAH).


RESTLESS LEGS SYNDROME

At least 20% of patients with chronic renal failure suffer from creeping, crawling, prickling, and pruritic sensations deep within the legs particularly when at rest and improving with movement (see Chapter 75). Periodic limb movements of sleep may coexist. Dialysis often does not lead to significant improvement, and treatment is similar to that in patients without renal failure.


BENIGN INTRACRANIAL HYPERTENSION

Benign intracranial hypertension or pseudotumor cerebri is thought to occur more frequently in patients with chronic renal failure (see also Chapter 107). Symptoms typically include headache, visual obscurations, and possibly sixth nerve palsies. Focal mass lesions and CSF infections must be excluded. Treatment consists of managing renal failure, weight loss, low-salt diet, and often diuretics, in particular, acetazolamide 500 mg orally (PO) three times a day (t.i.d.).


PERIPHERAL NEUROPATHY

The most common neurologic consequence of chronic renal failure is a distal, symmetric, predominantly axonal, mixed sensorimotor neuropathy affecting the legs more than the arms. Cranial nerves, particularly vision and hearing, and the autonomic nervous system may be affected. The rate of progression, severity, prominence of motor or sensory symptoms and signs, and degree of pain varies. Decreased vibratory and temperature sense in the feet are the earliest signs and sensory symptoms and signs usually predate motor. In general, the neuropathy evolves over several months but may be fulminant.


PATHOBIOLOGY

Pathologically, uremic neuropathy is usually a primary axonal degeneration with secondary segmental demyelination; there is also a predominantly demyelinating type. Because uremic neuropathy improves with hemodialysis, it seems likely that the neuropathy results from the accumulation of dialyzable metabolites. The control of neuropathy in some patients depends on increased hours of dialysis each week. The use of erythropoietin has also been reported to improve uremic neuropathy.




MYOPATHY

In patients with renal failure, myopathy with proximal limb weakness, fatigability, and atrophy is a poorly understood condition. Muscle enzymes and electromyogram (EMG) are usually normal. Muscle biopsy may reveal nonspecific alterations and sometimes type II fiber atrophy. Electrolyte abnormalities, in particular potassium, calcium, and magnesium, must be considered. If the patient has been treated with a kidney transplant and is taking steroids, a steroid myopathy may be considered.


NEUROLOGIC COMPLICATIONS OF RENAL TRANSPLANTATION

Renal transplantation is the preferred treatment of end-stage renal disease, and with advances in transplantation medicine, these patients live longer and are more at risk for the adverse consequences of long-term immunosuppression.

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Jul 27, 2016 | Posted by in NEUROLOGY | Comments Off on Renal Disease and the Brain
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