Open Journal Systems

MEDICAL SPECIALITIES

Received: October 22^nd 2014

Accepted: March 6^th 2015

Alterations in cerebral perfusion in patients with systemic sclerosis and cognitive impairment

Juan Moreno-Gutiérrez,^a Luis Alonso Coria-Moctezuma,^b María del Pilar Cruz-Domínguez,^c Olga Lidia Vera-Lastra^d

^aDepartamento de Medicina Interna

^bDepartamento de Medicina Nuclear

^cDivisión de Investigación

^dDepartamento de Medicina Interna

Hospital de Especialidades, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Distrito Federal, México

Communication with: Olga Lidia Vera-Lastra

Telephone: (55) 5724 5900, extensión 23161

Email: olgavera62@yahoo.com.mx

Background: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by fibrosis, immunological and vascular abnormalities. Cerebral hypoperfusion can be caused by cerebral ischemia. Cognitive impairment (CI) are a major cause of morbidity in SSc The aim of this study is to estimate the frequency of alterations in cerebral perfusion (CP) in SSc patients with CI.

Methods: We studied 88 patients with SSc. The Montreal Test (MT) was given to all patients to evaluate CI. To 15 patients with CI and without systemic hypertension, diabetes mellitus, cerebrovascular disease, vasculitis, hypothyroidism, depression, and drugs that interfere with the cognitive assessment, the PC was measured by cerebral gammagram (CG).

Results: Of the 88 patients with ES, 58 had CI by MT. A decrease in CP was observed in following lobes: frontal in 9 of 15 patients, temporal in 7 of 15, and parietal in 3 of 15. Concordance between MT and CG was 60 % for the frontal, 46 % for the temporal and parietal 13 %.

Conclusions: The CI is common in SSc. A decrease in CP was more frequent in the frontal lobe, predominating in older patients and with longer duration of SSc.

Keywords: Systemic sclerosis, Cerebral perfusion, Cognitive impairment, Gammagram cerebral.

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Systemic sclerosis (SS) is an autoimmune disease characterized by fibrosis and immune and vascular disorders with multisystem involvement. There are two forms of the skin disease: diffuse (generalized hardening of the skin), and limited (hardening of the face and distal extremities).^1-4

Lung disorders are the leading cause of morbidity and mortality. Neuropsychiatric disorders occur in up to 60% such as memory disorders, disorientation, depression, hallucinations, altered mental state, and cognitive impairment (CI). These are related to microvascular damage, but the pathophysiological mechanisms are little known.^5-10

The cognitive disorders include mild CI and dementia. The test of Montreal (TM) has a sensitivity of 90% and a specificity of 87%; the test evaluates multiple cognitive domains in various diseases with cerebral involvement, and is also useful for evaluating CI. A score ≥ 26 is considered within normal, 19-26 mild IC, and a score ≤ 21 dementia.^11-20

Cerebral perfusion scintigraphy (CPS) is useful to show decreased cerebral perfusion (CP) with 98% sensitivity and 80% specificity. CPS has been used to assess CP in autoimmune diseases.^21-25

The aim of this study was to determine the frequency of CP disorders using CPS in patients with SS and CI.

Methods

A cross-sectional study was conducted in the SS clinic at the Departamento de Medicina Interna of the Hospital de Especialidades, “Dr. Antonio Fraga Mouret”. Inclusion criteria were: SS diagnosis according to preliminary 1980 criteria of the American College of Rheumatology (ACR): diffuse and limited forms of SS, age over 18 and under 70, men and women with CI diagnosed by TM. Non-inclusion criteria: hypertension, diabetes mellitus, history of cerebral vascular event, history of intracranial or systemic tumors, neurological infection, autoimmune diseases: (overlap syndrome, antiphospholipid antibody syndrome, primary or secondary vasculitis of the central nervous system), brain trauma, chronic kidney disease, hypothyroidism, depression, drugs that interfere with cognitive evaluation, dyslipidemia, known allergies to iodine, and pregnancy. The protocol was approved by the hospital’s Research Committee. 

88 patients with SS were included. Data were obtained by interview, from the clinical record, and TM was applied to detect CI. TM results were analyzed and those with a score ≤ 26 points were diagnosed with CI. Of the 88 patients with SS, only 58 met the criteria for CI, and 15 patients were selected for CPS to be performed. CPS was performed with an 8-hour fast without consumption of vasodilators for the 24 hours before. The test was performed using single photon emission tomography to assess cerebral perfusion. CPS tests were interpreted by a specialist doctor in nuclear medicine, who reported the results as mild, moderate, and severe decreased perfusion, as well as its location.

For the analysis descriptive statistics and chi-squared were used.

Results

Demographic data of the 88 initials patients are seen in Table I. Of the 15 participants who met criteria for SS and CI, and who underwent CPS, 12 participants showed impaired perfusion, 80%, and 3 participants (20%) had no CP disorder.

The disorders found in the CPS were: frontal lobe 9/15 (60%), temporal lobe 7/15 (46%), parietal lobe in 3/15 (20%).

Of the patients with cognitive impairment, 50 (86%) had diffuse SS and 8 the limited variety (14%). Of the 15 patients who underwent CPS, 13 had diffuse forms versus 3 with limited.

Discussion

We studied 88 patients with SS, in 66% of whom TM found CI compared to 34% without CI. Of patients with CI, only 15 underwent CPS, finding decreased cerebral perfusion in up to 80% (12/15), with frontal lobe disorder predominating, followed by temporal.  

Our study found high frequency of CI using TM; however, when CPS was performed, the frequency of damage increased to 80%. It had previously been thought that psychiatric disorders in SS were rare. However, our study showed a high frequency of CI, in contrast with those reported in the literature that show presence of CI in about 10% of patients with SS.²⁶ The main disorders in our patients were found in the areas of attention, language, and delayed recall, which is similar to that reported by other studies.²⁷ 

In other autoimmune diseases such as systemic lupus erythematosus (SLE), CI has been reported in up to 50% of cases.^28-31 In patients with Sjögren's syndrome, CI is 60%, and in Multiple Sclerosis 76%.³²

Current studies show that with SS there may be involvement of the whole organism. It is thought that cognitive manifestations are caused mainly by disorders of cerebral perfusion.^5-10,33,34 CI may be multifactorial where there is involvement of: Raynaud's phenomenon, atherosclerosis, oxidative stress, and others. There are few studies of cerebral hypoperfusion in SS where figures of 52% have been found determined by single photon emission computerized tomography (SPECT) and 99mTc-hexamethylpropylenamineoxime (HMPAO).³⁵ There are also other studies of CP in patients with some autoimmune diseases (SLE and Behcet's disease), in one of these studies early and timely detection of these disorders was found useful because decreased CP was detected in asymptomatic patients, and then control CPS was done showing further deterioration, as well the presence of cognitive symptoms.²⁴  

In this study hypoperfusion was found predominant in the frontal lobe with a 60% relationship between CPS and TM, in the temporal lobe of 46%, while in the parietal it was of 20%. Some had more than one affected region. It was also shown that longer development of SS is associated with increased CI, and greater decrease in CP, and that the areas most involved were attention, language, and delayed recall. Moreover, it was observed that the patients with diffuse variety SS had greater CI than patients with the limited form. 

Cognitive disorders are major cause of morbidity and mortality, especially in patients with SS occurring with other systemic disorders. For these patients one should consider initiation of specific treatment, which could be the use of vasodilators such as nimodipine, citicoline (a precursor of phospholipid synthesis) and acetylcholine (which inhibits apoptosis associated with cerebral ischemia) in mild CI cases. These patients are also recommended oxidative stress measures (B complex, folic acid, nicotinic acid, vitamin C)^36-38 and exercises to improve brain activity.

Conclusions

In patients with SS, a high frequency of CI was found by TM and CPS. Cerebral hypoperfusion was more frequent in the frontal lobe. CI was more frequent in diffuse SS of longer duration.

Acknowledgements

To Dr. Emmanuel Gonzalez Vargas.

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