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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1998  |  Volume : 9  |  Issue : 4  |  Page : 435-439
Neurological Disorders in Renal Transplant Recipients


Sections of Nephrology and Neurology, King Fahad National Guard Hospital, Riyadh, Saudi Arabia

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   Abstract 

The charts of 175 renal transplant recipients were retrospectively reviewed. The mean duration of follow up since the transplantation was 4.17 ± 1.66 years. Apart from cyclosporin induced tremor, which occurred almost in all patients, 22 patients (12.5%) had neurological disorders during their follow up (mean annual incidence of 3%). Eight patients had epileptic seizures, seven had strokes, four had neurological infections, two developed a pseudotumor cerebri syndrome, two neuropathies, one myopathy and one conus medullaris infarction. This study demonstrates that neurological disorders are not uncommon in renal transplant recipients and that their mechanisms are variable and may be related to the underlying diseases such as hypertension and diabetes; to the operation itself; to the side effects of immunosuppression agents or rarely, they can accompany graft rejection.

How to cite this article:
Al Ghamdi G, Awada A, Tanimu DZ, Huraib SO, Romeh SA, Quadri K, Al Khudair W, Iqbal A. Neurological Disorders in Renal Transplant Recipients. Saudi J Kidney Dis Transpl 1998;9:435-9

How to cite this URL:
Al Ghamdi G, Awada A, Tanimu DZ, Huraib SO, Romeh SA, Quadri K, Al Khudair W, Iqbal A. Neurological Disorders in Renal Transplant Recipients. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2021 Apr 15];9:435-9. Available from: https://www.sjkdt.org/text.asp?1998/9/4/435/39102

   Introduction Top


Since the first transplant performed by Hume and his colleagues in the early 1950's [1] , renal transplant operations have become the best therapy for most patients with end­stage renal disease. More than 10,000 operations are performed each year and the 5-years patient survival rate has reached almost 90% in many centers. However, with increased survival, new diseases in the recipients are occurring and among these, neurological disorders are not infrequent [3] .

We reviewed all cases of renal transplant patients which were followed in our hospital over the last five years to estimate the frequencies and types of neurological disorders that has occurred in these patients and to compare our experience with those reported elsewhere.


   Patients and Methods Top


The nephrology section in our hospital keeps a computerized record of all renal transplant patients who have been, at one stage or another of their disease, examined in the hospital. All patients aged 15 years or more at the time of transplant were included. From a total of 175 patients recorded, 109 had received their transplanted kidney in our institution (cadaveric kidney in 79 cases (72%) and a kidney from a living related person in 30 cases (28%)). The other 66 patients were operated abroad including 55 (83%) who received kidneys from a non-related living person.

The charts of all these patients were reviewed and the following data extracted: age, sex, date and place of transplant, duration of follow up, presence of associated disorders such as hypertension or diabetes or any other relevant disorders before or after transplant. All neurological disorders occurring since the transplantation were also recorded.

The data were recorded on MS Office­Excel computer program and analyzed statistically.


   Results Top


The 175 patients included 104 male (59%) and 71 (41%) female. Their mean age ± SD was 38 ± 11 years (range 15-68). The mean duration of follow up was 4.17 years± 1.69. One hundred twenty eight patients (73%) were hypertensive and 28 (16%) diabetic. Some patients had neurological disorders before the transplantation and were not included.

Apart from cyclosporin induced tremor which occurred in all patients, 22 patients (12.5%) [Table - 1] had neurological disorders during their follow up, giving a mean incidence of 3/100 patients/year.

Eight patients (5%) had epileptic seizures, seven had strokes (4%) including five cerebral infarctions and two cerebral hemorrhages; four patients (2%) had neuro­logical infections (3 herpes zoster and one spinal tuberculosis), two (1%) developed symptoms and signs of pseudotumor cerebri, two developed neuropathies, one steroid induced myopathy and one patient developed a conus medullaris infarction post operatively.

In the eight cases of epilepsy, brain computed tomography revealed an underlying cerebral infarction in three cases. Brain CT and magnetic resonance imaging (MRI) were normal in the other cases. The two patients with pseudotumor cerebri were fully investigated by lumbar puncture, cerebral MRI and angiography and no clear cause was found particularly, there was no cerebral sinus occlusion and no meningitis. One of the neuropathy cases was indirectly related to the renal transplantation. This patient developed a systemic non-Hodgkin lymphoma and his neuropathy was secondary to vincristin treatment.

Four patients died from their neurological disorders: the two cases who developed cerebral hemorrhage, one case with cerebral infarction and one patient with severe neuropathy.


   Discussion Top


Neurological disorders have been estimated to occur in up to 30% of renal transplant recipient over an 18-year period in the USA [4] . These disorders were less frequent in our patients but duration of follow up was also much shorter.

Neurological disorders in renal transplant recipients could be divided into four categories: i) those related to the underlying diseases such as hypertension or diabetes; ii) those related to the operation itself; iii) those related to the immunosuppressive agents and iv) those associated with graft rejections.

Most of our transplant ant patients were hypertensive and 16% of them were diabetic. It is thus not unexpected that 4% of them developed strokes in the study period. The rate of cerebral infarct was reported to vary between 4% over six year's [5] to 6.2% over 18 year's [4] . In com­parison, incidence rate of strokes in the general population is 0.15 to 0.5% per year in western countries and Japan ' while it has been found to be 0.03% in Saudi Arabia [8] . In addition to hypertension and diabetes mellitus, which are the two main risk factors for cerebral infarction, it has been suggested that prolonged corticosteroid therapy provokes hypercoagulability [9] . Of course, renal transplant patients who are affected by connective tissue diseases are also prone to cerebral infarcts but this was not the case in our patients. On the other hand, cerebral hemorrhage has been described in renal transplant recipients and the role of hypertension, as in cerebral infarcts is prominent. Three of the 467 patients of Adams et al developed cerebral hemorrhage. All three of them were hyper­tensive as were our two patients. Another potential cause of intracranial hemorrhage in renal transplant recipients is the presence of berry aneurysms, which are associated with polycystic kidney disease in 10-20% of the cases. Eight of our patients (4.6%) developed epileptic seizures over the study period. This again, is much higher than the incidence of epilepsy in the community, which is around 0.01% per year in the west [10] and unknown but probably within the same frequency in Saudi Arabia. Of course, cerebral infarcts or hemorrhages can lead to symptomatic epileptic seizures, especially in those patients under cyclosporin, which is known to lower the epileptic threshold [11] .

Neurological complications due to renal transplant procedures are rare. The most common of them result from venous, arterial or nerve injury. Peripheral nerve injuries can involve the femoral and the lateral femoral cutaneous nerve [12] .In few patients, with arterial anatomical variations, an ischemia of the caudal spinal cord can occur. This happened in one of our patients but was fortunately transient. It is believed that in those patients, the caudal cord is supplied by branches of the internal iliac artery, which is used to supply blood to the allograft, rather than by the intercostals artery. [13]

Immunosuppressive agents carry their own neurological adverse effects. Tremor is very common with cyclosporin and our patients developed tremors when they were on a high dose, early after transplantation. Cyclosporin is also known to be epileptogenic and seizures have been reported to occur in 2-6% of patients who are receiving this medication [11] . Seizures occurred in three of our patients with cerebral infarction, and also in another five, whose CT was absolutely normal. Two other patients were known to be epileptic before transplantation and continued to develop occasional seizures despite anti epileptic treatment. None of the patient developed cyclosporin encephalopathy.

The other immunosuppressive drugs, which were used systemically in our patients, were azathioprine and prednisone. Many patients had the usual side effects of long-term steroid use but in one case, the steroid induced myopathy was so severe that the patient became wheelchair bound. Two other patients developed a pseudotumor cerebri syndrome, in which steroids probably played a role. This complication has been very rarely described in renal transplant patients and these two cases were reported in another paper [14] .

Immunosuppressive drugs would also predispose to opportunistic infections of the nervous system. Fortunately, none of our patients developed severe meningitis or encephalitis. However, three of them developed herpes zoster infection and one had a tuberculous abscess of the spine with secondary spinal cord compression and paraparesis. This responded well to antituberculous drug therapy. Development of malignancies is also another important complication of prolonged immunosuppression. Non-Hodgkin lymphomas and more particularly primary central nervous system lymphomas have been commonly reported. [15] One of our patients developed a systemic non-Hodgkin lymphoma, which was complicated by a severe vincristin-induced neuropathy.

Finally, a syndrome of encephalopthy associated with acute rejection of the renal allograft has been described. [16] Besides the systemic manifestation of fever, swelling and tenderness of the graft and renal failure, these patients would present with head­aches, stupor and convulsions. Some of our patients had acute graft rejection but we did not observe the neurological component of this syndrome in any of them.

In conclusion, his study, like the few previously published studies on the same subject [4],[5], demonstrates that neurological disorders in renal transplant recipients are not uncommon and occur at an annual rate of approximately 3%. Some of them are common to most organ transplants such as those related to immunosuppression and immunosuppressive agents. Others are more specific to renal transplant patients who are usually prone to vascular compli­cations in the form of cerebrovascular disease and as a specific complication of the transplant procedure itself. A better selection of patients and better understanding of the mechanism of complications will help in preventing many of them. Aware­ness of these complications would also help in recognizing and treating them promptly.

 
   References Top

1.Hume DM, Merrill JP, Miller BF, Thorn GW.Experiences with renal homotransplantation in the human: report of nine cases. J Clin Invest 1955;34:327-82.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Keown PA, Shackleton CR, Ferguson BM.Long-term mortality, morbidity and rehabilitation in organ transplant recipients. In: Leendert PC, Soleh K (eds), Organ Transplantation: long term result. New York, Marcel Dckker 1992;57-84.  Back to cited text no. 2    
3.Patchell RA. Neurological complications oforgan transplantation. Ann Neurol 1994;36: 688-703.  Back to cited text no. 3  [PUBMED]  
4.Adams HP Jr, Dawson G, Cofrman TJ; CorryRJ. Stroke in renal transplant recipients. ArchNeurol 1986;43:113-5.  Back to cited text no. 4    
5.Venkateswara K, Smith EJ, Alexander JW,Fidler JP, Pemmaraju SR, Pollack VE. Throm-boembolic disease in renal allograft recipients. What is its clinical significance? Arch Surg 1976;lll:1086-92.  Back to cited text no. 5    
6.Bonita R. Epidemiology of stroke. Lancet 1992;339:342-4.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Tanaka H. Age-specific incidence of strokesubtypes in Shibata, Japan. Stroke 1982;13:110.  Back to cited text no. 7  [PUBMED]  
8.Al Rajeh S, Larbi E, Bademosi O, et al. Strokeregister: experience from the Eastern province of Saudi Arabia. Cerebrovasc Dis. 1998;8:86-9.  Back to cited text no. 8    
9.Ozsoyhi S, Strauss HS, Diamond LK. Effects of corticosteroids on coagulation of the blood. Nature 1962;195:1214-5.  Back to cited text no. 9    
10.Hauser WA, Annegers JF, Rocca WA.Descriptive epidemiology of epilepsy: contributions of population-based studies from Rochester, Minnesota. Mayo ClinProc 1996;71: 576-86.  Back to cited text no. 10    
11.Walker RW, Brochstein JA. Neurologic complications of immunosuppressive agents. NeurolClinl988;6:261-78.  Back to cited text no. 11    
12.Junaid I, Kwan JT; Lord RH. Femoral neuropathyin renal transplantation. Transplantation 1993; 56:240-1.  Back to cited text no. 12    
13.Jablechi CK, Aguilo JJ, Piepgras DG.Paraparesis after renal transplantation. AnnNeurol 1977;2:154-5.  Back to cited text no. 13    
14.Obeid T, Awada A, Huraib S, Quadri K,Abu Romeh S. Pseudotumor cerebri in renal transplant recipients. A diagnostic challenge. J Nephrol 1997;10(5):258-60.  Back to cited text no. 14    
15.Patchell RA. Primary central nervous systemlymphoma in the transplant patient. Neurol Clin 1988;6:297-303.  Back to cited text no. 15  [PUBMED]  
16.Gross ML, Sweny P, Pearson RM, Kennedy J,Fernando ON, Moorhead JF. Rejection encephalopathy. An acute neurological syndrome complicating renal transplantation. J Neurol Sci 1982;56:23-34.  Back to cited text no. 16    

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Correspondence Address:
Ghormullah Al Ghamdi
Consultant Nephrologist, Division of Nephrology & Hypertension, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426
Saudi Arabia
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PMID: 18408314

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    Abstract
    Introduction
    Patients and Methods
    Results
    Discussion
    References
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