Neurological Manifestations of Uremic Encephalopathy Workup

Updated: Sep 17, 2018
  • Author: Gabriel Bucurescu, MD, MS; Chief Editor: Jasvinder Chawla, MD, MBA  more...
  • Print

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.


Imaging Studies

Brain imaging is of limited value. However, case reports exist of isolated cortical, centrum semiovale, basal ganglia, and brainstem involvement revealed by magnetic resonance imaging. The scans of such patients may show high signal either on diffusion-weighted imaging (WDWI) or on fluid-attenuated inversion recovery (FLAIR) imaging. [8, 9]

Brain SPECT is of limited benefit, however, a recent article describes a uremic patient with end-stage renal failure with bilateral basal ganglia decreased uptake. The patient had Parkinsonism, which was attributed to complications from uremia. [10]


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 encephalopath 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 encephalopath 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.
  • 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. [11]

  • 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. [12]

  • 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.



See the list below:

  • Hemodialysis

  • Peritoneal dialysis

  • Renal transplantation

  • Neurosurgical intervention for intracranial hemorrhage or subdural hematoma


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.