UE is an uncommon neurological complication. As a metabolic encephalopathy, it is a clinical syndrome caused by endogenous uremia toxin. It is characterized by various acute or subacute neurological symptoms resulting from brain edema, and is usually reversible [1, 6, 10]. Clinically, UE may manifest as a series of neurological abnormalities, ranging from mild attention loss to coma, and can be further characterized by headache, sleep, articulation, and gait disorders. It is less associated with extrapyramidal movement including involuntary movement, bradykinesia, tremor, epileptic activity, chorea and Parkinson’s disease [2,3,4]. The clinical manifestation of our case was involuntary movement, presenting at first with resting shoulder and neck tremor which became increasingly serious, progressing to involuntary limb movement. The patient had no complaints of headache, fever, blurred vision or mental disorder.
As outlined, UE can be classified into three types, based on brain imaging results. Firstly, UE may involve cortical or subcortical regions, which is more common and may develop in any uremic patient, with no effect of DM. When affecting the cortical region, UE can cause reversible posterior leukoencephalopathy syndrome [2, 5, 6]. Secondly, UE may involve the basal ganglia, which is uncommon, although previous cases have reported that Asian patients with DM usually present with basal ganglia injury [2, 6, 7]. Finally, UE may involve white matter, which is rare subtype that is limited to case reports [5, 8]. The main radiological manifestation of UE with cortical involvement is vasogenic edema, whereas that of UE with basal ganglia involvement is both cytotoxic and vasogenic edema . Some studies have reported that non-diabetic UE may lead to the development of some unusual neurologic symptoms, such as facial palsy. The imaging findings of non-diabetic UE are unique and atypical, such as only supratentorial white matter lesions, no cortex or basal ganglia involved . The neuroimaging results in our case showed typical bilateral basal ganglia lesions, which were reversible and characterized by symmetrical T2WI and T2FLAIR hyperintense nonhemorrhagic lesions. Additionally, corona radiata lesions were also found, and showed mild diffusion restriction and both T1WI and DWI displaying normal signals. Usually, imaging findings such as these are reported in uremic patients along with DM, who develop acute dyskinesia in the context of a significant fluctuation in blood glucose levels (predominantly hyperglycemia) and severe uremia. However, the patient in this case did not suffer from DM and had steady blood glucose levels.
The pathogenesis of UE is complex and remains unclear, and in which neurotoxic compounds are likely to play an important role. Many factors including uremia, parathyroid hormone, metabolic acidosis, abnormal blood glucose, methylguanidine, aluminum poisoning, abnormal osmotic pressure and insufficient blood supply in the brain are considered as possible causative factors [7, 10, 12, 13]. Vanholder et al. reported that uremic toxins play a pathogenic role might through stimulating N-methyl-D-aspartate receptors and inhibiting γ-aminobutyric acid receptors. The symptoms might therefore be due to an alteration in the balance between excitatory and inhibitory amino acids and the disruption of polysynaptic pathways . Furthermore, previous studies have also suggested some possible mechanisms of UE. First, a significant fluctuation in blood glucose levels (predominantly hyperglycemia) in diabetic uremic patients can increases the permeability of the blood-brain barrier. Due to cerebrovascular endothelial dysfunction (so-called dysfunction in the automatic regulation of blood vessels), uremic toxins are able to inhibit mitochondrial function, leading to destruction of the pallidum and putamen. This is seen in DM, where the basal ganglia becomes more susceptible to neurotoxic compounds . Second, excessive uremic metabolic wastes may damage brain tissue, among which the basal ganglia is the most vulnerable, particularly in areas that have suffered from the obstacle of vascular autoregulation, impaired energy utilization and microangiopathy. Third, a significant decrease in cerebral oxygen consumption in uremia patients may lead to cellular edema due to disordered focal cellular metabolism [1, 5,6,7, 10, 11]. One study analyzed biochemical indicators of UE during the “pre-symptomatic” period. The results showed that these diabetic and nephrotic patients had metabolic acidosis and obvious biochemical indicators 2 weeks before admission. Therefore, the investigators assumed that the pre-clinical internal environment may play an important role in the pathophysiology of UE . As most previous studies have reported, after renal failure has been treated and a decrease in the level of uremic toxins is achieved, clinical symptoms generally go into remission or complete recovery, and lesions seen in neuroimaging tests are lightened or disappear altogether. However, the long-term prognosis of UE remains poor according to some reports, with some patients requiring long-term intensive care on account of UE related complications, but UE itself does not. The prognosis of those basal ganglia damage or diabetic UE patients is even poorer [10, 16].
We assumed that our case may have been caused by the breakdown of the blood-brain barrier, related to the observed increase in uremic toxins, which measured as follows: urea nitrogen 25.80 mmol/L, creatinine 1206 μmol/L, uric acid 548 μmol/L, phosphorus 1.88 mmol/L, calcium 2.33 mmol/L. Moreover, the patient exhibited extreme hyperthyroidism with an iPTH of almost 3200 pg/mL 5 days prior to admission, declining to 2487 pg/mL after admission to our hospital. After treatment with high frequency and high flux dialysis (4 h hemodiafiltration with APS, four times per week), hyperbaric oxygen therapy (1.5 h per day), declining parathyroid hormone (1 μg of calcitriol injection every 2 days), and treatment for symptom relief (2 mg of haloperidol, 2 mg of clonazepam and 2 mg of benzhexol, administered orally twice per day), the clinical symptoms of the patient resolved gradually, with a decrease in both the frequency and amplitude of involuntary movement. Once the symptoms had achieved partial remission, follow-up MRI images acquired 14 days later showed high signal in the bilateral basal ganglia region on T2WI and T2FLAIR, which were nevertheless significantly weaker than the former MRI signal. About 1 month later, blood test results showed relatively stable uremic toxins (urea nitrogen 10.48 mmol/L, serum creatinine 641.5 μmol/L, uric acid 435 μmol/L, phosphorus 1.43 mmol/L, calcium 2.30 mmol/L,anion gap 15.9 mmol/L), and relieved hyperthyroidism (iPTH 1609 pg/mL). Finally, the patient achieved complete remission with normal body movement, and brain MRIs taken upon discharge showed an almost complete resolution of the lesions with slightly hyperintense signal on T2WI and T2FLAIR.
UE is an unfamiliar toxic metabolic encephalopathy with typical CT/MR neuroimaging showing bilateral vasogenic or cytotoxic edema in the cerebral cortex or basal ganglia region, producing a series of neurological abnormalities, ranging from mild attention loss to coma. UE with basal ganglia injury is uncommon, and generally occurs in Asian patients with DM. In our case, the patient had non-diabetic UE with typical bilateral basal ganglia lesions, and presented with involuntary movement. Recognizing this syndrome is of increasing importance, especially considering its diagnostic and prognostic implications.