Neurological Manifestations of Uremic Encephalopathy Workup

  • Author: Gabriel Bucurescu, MD, MS; Chief Editor: Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA   more...
 
Updated: Aug 17, 2010
 

Laboratory Studies

  • Blood tests reveal electrolyte abnormalities and abnormal renal function. PTH and calcium levels are high.
  • Results of routine CSF studies tend to be normal.
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Imaging Studies

  • Brain imaging is of limited value.
  • CT and MRI studies typically show cerebral atrophy and secondary ventricular dilatation.
    • These studies are valuable for excluding intracranial hemorrhage and subdural hematoma when patients have an acute change in mental status.
    • Case reports have documented increased signal intensity in the cortical and subcortical areas of the parietal and occipital lobes. These findings are thought to reflect local edema that resolved after dialysis treatments. Improvement on MRI has been correlated with improved serum creatinine and BUN levels.
    • Several recent case reports mentioned bilateral basal ganglia lesions in uremic patients with diabetes, characterized by high signal intensities on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. These lesions resolved after intensified dialysis and correlated with a decrease in serum blood urea nitrogen and creatinine levels.[5]
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Other Tests

  • EEG (especially serial EEG) is useful in assessing patients and in monitoring their progress.
    • The EEG is generally abnormal, showing generalized slowing that becomes more severe as the condition worsens.
    • In acute uremia, EEG is characterized by irregular low voltage with slowing of the posterior dominant alpha rhythm and occasional theta bursts. Characteristic findings are prolonged bursts of bilateral, synchronous slow and sharp waves or spike and waves.
    • Bilateral spike discharges may be associated with myoclonic jerks. Generalized or partial seizures may be observed.EEG in a 56-year-old man with uremic encephalopathEEG in a 56-year-old man with uremic encephalopathy. He became increasingly lethargic, requiring intubation. EEG shows absence of a posterior dominant alpha rhythm and diffuse bilateral slowing with mixed theta- and delta-frequency signal. A single sharp wave is present in the left occipital region, phase reversing at O1. From top to bottom: Fp1-F7, F7-T3, T3-T5, T5-O1, O1-O2, O2-T6, T6-T4, T4-F8, F8-Fp2, Fp2-Fp1, F3-C3, C3-P3, P3-O1, F4-C4, C4-P4, P4-O2, Fz-Cz, and ECG. EEG in a 56-year-old man with uremic encephalopathEEG in a 56-year-old man with uremic encephalopathy. From top to bottom: Fp1-F7, F7-T3, T3-T5, T5-O1, Fp2-F8, F8-T4, T4-T6, T6-O2, Fp1-F3, F3-C3, C3-P3, P3=O1, Fp2-F4, F4-C4, C4-P4, P4-O2, Fz-Cz, ECG.
    • After dialysis begins, EEG may worsen for up to 6 months before slowly normalizing as renal function improves. Dialysis itself tends not to affect the EEG.
    • In chronic uremia, the EEG stabilizes during long-term dialysis treatment. When changes occur during periods of deterioration corresponding to fluctuations in blood urea levels, the findings include diffuse delta and theta activity, generalized spike-wave activity, and heightened sensitivity to photic stimulation.
    • Quantitative EEG using real-time brain mapping computer-aided topographical electroencephalometry (CATEEM) technology has been shown to be useful in monitoring mental impairment and may serve as a control for monitoring therapeutic intervention.[6]
    • Sleep EEG may show long bursts of high voltage (12-13 waves per second with enhanced vertex sharp activity in drowsiness), lack of spindles (14/s) in stage 2 sleep, and prolonged high-voltage, slow bursts with awakening.
  • Evoked-potential studies are of limited value, revealing only nonspecific changes or normal patterns.
    • Visual evoked potentials (VEPs): Studies may reveal no change before or after dialysis, or P100 may be absent or delayed. This abnormality is attributed to a circulating renal factor, which has a toxic effect on the papillomacular bundle or on demyelination. No relationship with BUN is known.
    • Brainstem auditory evoked potentials (BAEPs): Some studies of patients with UE show no abnormalities in BAEPs, whereas other studies of small numbers of patients revealed abnormalities, especially in the III-IV latencies. The abnormalities reversed with dialysis in some patients and did not reverse in others. Changes in BAEP were attributed to either toxic substances or demyelination. Other studies measuring the P300 latency and amplitude have shown improvement in patients with UE who were specifically treated for anemia. The improvement in the electrophysiological parameters accompanied improvement in cognitive function, suggesting that measurements of P300 may serve as a measurable marker for cognitive function.[7]
    • Somatosensory evoked potentials (SEPs): Studies may show delayed sensory conduction in the peripheral nerve in patients with no symptoms of neuropathy. This was observed in the upper limb with electrically and mechanically evoked SEPs.
      • In 1 study, electrical stimulation of the ulnar nerve at the wrist showed abnormal conduction between the brachial plexus and the spinal cord and lower medulla. Other studies revealed abnormal conduction between the lower medulla and the thalamus and cortex.
      • Mechanical stimulation of the fingers showed abnormalities in the spinal cord to thalamus-cortex segment, whereas electrical stimulation did not.
      • Some studies revealed central delays and increased amplitudes in patients with chronic uremia, whereas others showed normal central conduction times in patients undergoing hemodialysis.
      • Abnormalities were observed in both upper- and lower-limb SEPs in patients with chronic renal failure.
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Procedures

  • Hemodialysis
  • Peritoneal dialysis
  • Renal transplantation
  • Neurosurgical intervention for intracranial hemorrhage or subdural hematoma
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Histologic Findings

Brain histologic findings in UE include meningeal fibrosis, glial changes, edema, vascular degeneration, focal and diffuse neuronal degeneration, and focal demyelination. Small infarcts are also seen and are probably due to hypertension or focal necrosis. Cerebellar acute granule cell necrosis is observed.

Patients with dialysis dementia have spongiform changes in the outer 3 cortical layers, with elevated aluminum levels in the cerebral cortex. Other changes include neuronal loss, accumulation of lipofuscin pigment, and neurofibrillary degeneration in the motor cortex and in the red, dentate, and olivary nuclei.

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Contributor Information and Disclosures
Author

Gabriel Bucurescu, MD, MS  Staff Neurologist, Neurology Service, Philadelphia Veterans Affairs Medical Center

Gabriel Bucurescu, MD, MS is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, and American Epilepsy Society

Disclosure: Nothing to disclose.

Specialty Editor Board

J Stephen Huff, MD  Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Richard J Caselli, MD  Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale

Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi

Disclosure: Nothing to disclose.

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA  Associate Dean, College of Medicine, Professor of Neurology, Neurosurgery and Psychiatry, Director of Cognitive Neurology, Department of Neurology, University of South Florida College of Medicine; Director of Stroke Service, Tampa General Hospital; Director of Stroke Program, James A Haley Veterans Affairs Hospital

Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA is a member of the following medical societies: American Academy of Neurology, American Headache Society, American Heart Association, and American Society of Neuroimaging

Disclosure: Nothing to disclose.

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EEG in a 56-year-old man with uremic encephalopathy. He became increasingly lethargic, requiring intubation. EEG shows absence of a posterior dominant alpha rhythm and diffuse bilateral slowing with mixed theta- and delta-frequency signal. A single sharp wave is present in the left occipital region, phase reversing at O1. From top to bottom: Fp1-F7, F7-T3, T3-T5, T5-O1, O1-O2, O2-T6, T6-T4, T4-F8, F8-Fp2, Fp2-Fp1, F3-C3, C3-P3, P3-O1, F4-C4, C4-P4, P4-O2, Fz-Cz, and ECG.
EEG in a 56-year-old man with uremic encephalopathy. From top to bottom: Fp1-F7, F7-T3, T3-T5, T5-O1, Fp2-F8, F8-T4, T4-T6, T6-O2, Fp1-F3, F3-C3, C3-P3, P3=O1, Fp2-F4, F4-C4, C4-P4, P4-O2, Fz-Cz, ECG.
 
 
 
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