Cognitive functions in multiple sclerosis patients

El-Sayed Ali Tag El-din; Wafik S Bahnasy; Khaled H Rashed; Eman R Abd El-Samad; Atef H Teama

ORIGINAL ARTICLE

Year : 2016 | Volume : 53 | Issue : 3 | Page : 168-173

Cognitive functions in multiple sclerosis patients

El-Sayed Ali Tag El-din¹, Wafik S Bahnasy¹, Khaled H Rashed¹, Eman R Abd El-Samad¹, Atef H Teama²
¹ Department of Neuropsychiatry, Tanta University, Tanta, Egypt
² Department of Diagnostic Radiology, Tanta University, Tanta, Egypt

Date of Submission	09-Jun-2015
Date of Acceptance	05-Dec-2015
Date of Web Publication	27-Oct-2016

Correspondence Address:
Wafik S Bahnasy
Department of Neuropsychiatry, Tanta University, Tanta, 11511
Egypt

Source of Support: None, Conflict of Interest: None

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Abstract

Background Cognitive impairment (CI) is a common manifestation of multiple sclerosis (MS) and can occur early or late in the disease course.
Objective The aim of this study was to evaluate the types and severity of CI in different MS subtypes.
Patients and methods This study was conducted on 40 MS patients and 20 healthy controls. Physical disability was assessed using the Expanded Disability Status Scale and cognitive functions were assessed using the Montreal Cognitive Assessment, the Wechsler Memory Scale-Revised, the Wisconsin Card Sorting Test, and the Bender-Gestalt test. Event-related potential p300, MRI, and brain magnetic resonance spectroscopy (MRS) were also performed.
Results There was significant CI in MS patients when compared with controls. The most commonly affected cognitive domain was information-processing speed, which led to impairment in memory, attention, and visuospatial and executive functions. MRS showed decreased N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) ratios and increased Cho/Cr ratio in MS patients. Secondary progressive multiple sclerosis patients seemed to have more CI compared with other types.
Conclusion CI is a common MS manifestation occurring early in the disease course and in all MS subtypes. The degree of CI is positively correlated with axonal loss in MRS, as evidenced by reduction in NAA/Cr ratio.

Keywords: cognitive impairment, event-related potential, magnetic resonance spectroscopy, MRI, multiple sclerosis, neuropsychological testing

How to cite this article:
Tag El-din ESA, Bahnasy WS, Rashed KH, Abd El-Samad ER, Teama AH. Cognitive functions in multiple sclerosis patients. Egypt J Neurol Psychiatry Neurosurg 2016;53:168-73

How to cite this URL:
Tag El-din ESA, Bahnasy WS, Rashed KH, Abd El-Samad ER, Teama AH. Cognitive functions in multiple sclerosis patients. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2023 Nov 28];53:168-73. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/3/168/193067

Introduction

Cognitive functions comprise a group of mental processes that allow an individual to perform everyday functions such as attention, memory, language, and executive functions, which include reasoning, problem solving, decision making, visuoconstructional skills, conceptual thinking, calculations, and orientation [1].

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that affects over 2.5 million people worldwide and is one of the most common causes of serious neurological disabilities in young adults [2]. Physical disabilities have been extensively studied in MS; yet cognitive impairments (CIs) are still under-researched despite their high incidence and significant impact on the patient’s quality of life [3].

Event-related potential (ERP) is an objective tool for evaluating certain aspects of cognitive processing [4]. Also, magnetic resonance spectroscopy (MRS) allows better understanding of the basis of CI in MS. It can detect metabolic abnormalities that often precede structural changes and can be used to follow-up disease progression and monitor therapeutic response [5].

Aim of the work

The aim of the study was to investigate cognitive functions in patients with MS and their relations to the severity of physical disability and disease subtype.

Patients and methods

The study included 40 patients with definite MS as per the Polman et al. [6] criteria who attended the Department of Neuropsychiatry, Tanta University Hospital, during the period 1 July 2011 to 1 October 2013. In addition, 20 age-matched, sex-matched, and education-matched healthy individuals were included. Written consent was taken from patients and controls. The Research Ethics Committee of Tanta University Hospital approved the study. Patients having a disease affecting cognition or with contraindications to MRI were excluded from the study.

Patients and controls were subjected to full history taking and to thorough general and neurological examination using the neurological sheet of the Tanta Neuropsychiatry Department. Physical disability was assessed using the Kurtzke Expanded Disability Status Scale (EDSS) [7].

A battery of standardized neuropsychological tests covering different cognitive domains was selected, which included the Montreal Cognitive Assessment (MoCA) [8], the Wechsler Memory Scale-Revised (WMS-R) [9], the Wisconsin Card Sorting Test (WCST) [10], and the Bender-Gestalt (BG) test [11].

ERPs p300 were determined in a sound-treated room using Tracoustic Model No RE. 241 (Carolinas Sales and Service’s, 480 Hillsboro St, Ste 100, Pittsboro, NC 27312, North Carolina, USA). Pure tone audiometry was performed using GSI version 61, and immittancemetry using Interacoustic AT235H and smart EPs of intelligent hearing system software version Microsoft Windows [4].

MRI scans were taken using 1.5-T unit SYS #GEMSOW. Single voxel localization proton MRS was performed using a spin-echo mode sequence with long TE (TR/TE/average=1600/144) and short TE (TR/TE=1600/35). Water suppression was achieved with chemical shift selection technique. The size of voxels was ∼8 cm³; the voxels were placed on the chosen MS lesions away from the cerebrospinal fluid and scalp fat and others were placed in the normal-appearing white matter. Voxels of the same size were placed over the parieto-occipital periventricular white matter in the control group. The metabolites were identified and the number of peaks fitted included the chemical shift ranges restricted to 1.9–2.1 ppm for N-acetyl aspartate (NAA), 2.9–3.1 ppm for creatine (Cr), and 3.1–3.3 ppm for choline (Cho). The peak ratios were calculated from the integration of the single peak, including NAA/Cr, NAA/Cho, and Cho/Cr.

Statistical presentation and analysis was conducted using mean, SD, the Student t-test, linear correlation coefficient, and analysis of variance tests with SPSS V18.

Results

The study included 40 MS patients: 20 with relapsing remitting multiple sclerosis (RRMS), 16 with secondary progressive multiple sclerosis (SPMS), and four with primary progressive multiple sclerosis (PPMS). Twenty-eight patients (70%) were female and 12 (30%) were male. The mean age was 33.8±10.02 years. The mean years of education was 12.45±3.08. Disease duration was 6.33±3.49 and the mean EDSS was 4.15±2.14. Twenty-three patients (57.5%) had CI with total MoCA score less than 26.

Clinical examination of the patient group revealed 16 cases (40%) with speech difficulties, 28 cases (70%) with either unilateral or bilateral optic atrophy, two cases (5%) with partial tertiary palsy, four cases (10%) with internuclear ophthalmoplegia, and 12 cases (30%) with nystagmus. Ten cases (25%) had impaired coordination, 30 cases (75%) had pyramidal signs, 10 cases (25%) had deep sensory impairment, 16 cases (40%) had urge incontinence, six male cases had weak erection, and two cases (5%) had diabetes mellitus.

The MoCA test among MS patients and controls showed significant difference in the total score (23.56±3.6 and 29±0.79, respectively) as well as in all subdomain scores except orientation, as described in [Table 1].

Table 1: Neuropsychological tests among multiple sclerosis patients and controls

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Regarding WMS-R, the four selected items showed significant decrease among MS patients when compared with controls. Mental control was 5.5±1.59 in MS patients compared with 8.6±0.68 in controls, whereas logic memory was 9.08±2.16 in MS patients compared with 15.3±0.87 in controls. Digit total was lower in MS patients than in controls (8.85±1.76 and 14.3±0.47, respectively). Associate learning was significantly diminished in MS patients than in controls (13.73±2.6 and 18.9±0.99, respectively), as shown in [Table 1].

In WCST, there was significant increase in preservative error in MS patients (11.6±6.2) compared with controls (6.7±1.45). Regarding conceptual level response, there was a significant decrease in MS patients (41.2±8.8) compared with controls (50.3±2.3). Testing trials to complete the first category showed a nonsignificant difference between MS patients (13±4.4) and controls (12.1±1.2) [Table 1].

Regarding the BG test, the copy part showed significant decrease in MS patients compared with controls (22.8±3.46 and 29.5±0.95, respectively). The recall part was also lower in MS patients than in controls (16.3±5.87 and 28.9±1.62, respectively), as shown in [Table 1].

Examination of ERP p300 showed significant prolongation of latencies in the right and left ears of MS patients (348.75±25.67 and 344.13±27.56) when compared with controls (305.38±28.77 and 301.19±31.48). ERP amplitudes were also lower in the right and left ears of MS patients (4.43±3.2 and 4.38±3.12) than in controls (9.36±3.98 and 9.13±4.16), as shown in [Table 2] and [Figure 1].

Table 2: Event-related potential p300 and magnetic resonance spectroscopy among multiple sclerosis patients and controls

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Figure 1: Event-related potential p300 of a female relapsing remitting multiple sclerosis (RRMS) patient aged 42 years; left ear latency 333, amplitude 2.77 (a), and right ear latency 309, amp 2.74 (b).

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MRI distribution of the MS plaques revealed that 28 patients (70%) had periventricular lesions, 26 (65%) had juxtacortical plaques, 10 patients (25%) had plaques in the corpus callosum, six patients (15%) had cerebellar plaques, six patients (15%) had plaques in the basal ganglia, four patients (10%) had plaques in the brainstem, and finally four patients (10%) had spinal cord lesions.

[Table 2] shows MRS among MS patients and controls with mild but statistically significant decrease in NAA/Cr ratio in MS patients (1.135±0.248) when compared with controls (1.485±0.185). There was also a statistically significant decrease in NAA/Cho ratio in MS patients (0.886±0.230) when compared with controls (1.273±0.105). In contrast, there was a statistically significant increase in Cho/Cr ratio in MS patients (1.814±0.283) compared with controls (1.166±0.102). Low NAA indicates axonal loss or dysfunction, whereas increased Cr and Cho suggest ongoing gliosis and remyelination.

The comparison between different MS subgroups showed that patients with SPMS had lower performance in neuropsychological tests and longer latencies and reduced amplitudes in ERP p300 compared with patients with PPMS and RRMS. Regarding MRS, NAA/Cr and NAA/Cho were significantly reduced, whereas Cho/Cr was significantly increased in SPMS compared with PPMS and RRMS [Table 3].

Table 3: Neuropsychological tests, event-related potential p300 and magnetic resonance spectroscopy among different multiple sclerosis subgroups

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There were inverse correlations between physical disability of MS patients measured by EDSS and each of total MoCA score [Figure 2], all subdomains of WMS-R, recall part of the BG test [Figure 3], amplitude of ERP p300, and MRS Cho/Cr ratio. There were positive correlations between EDSS of MS patients and each of perseverative errors of WCST, latency of the ERP p300, and MRS NAA/Cr and NAA/Cho ratios. The results of this study showed that total MoCA score as a measure of the degree of CI has a direct positive correlation with each of NAA/Cr and NAA/Cho in MRS as well as in the amplitude of ERP p300. In contrast, total MoCA has inverse correlation with MRS Cho/Cr and ERP p300 latencies.

Figure 2: Magnetic resonance spectroscopy (MRS) of a healthy person (a): multiple sclerosis (MS) lesion (b) and normal-appearing white matter (NAWM) of the same patient (c) at TE of 144; there is mildly decreased NAA/Cr, decreased NAA/Cho, and increased Cho/Cr ratios in both MS plaque and NAWM in comparison with normal controls.

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Figure 3: Inverse correlation between Expanded Disability Status Scale (EDSS) and each of total Montreal Cognitive Assessment (MoCA) score (left) and recall part of Bender-Gestalt test.

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Discussion

This study stated that CI in MS patients is 57.5%, which is in agreement with the results of Glanz et al. [12], who found that CI in MS patients ranges from 50 to 70%.

The mean age of MS patients in this study was 33.8±10.02 years; the mean disease duration was 6.33±3.5; 70% of patients were female; 50% had RRMS, 40% had SPMS, and 10% had PPMS. Regarding physical disability, the mean EDSS was 4.15±2.14. These results are in agreement with those of Ribeiro et al. [13].

This study revealed significant CI in MS patients measured by different neuropsychological scales and also by auditory ERP p300. There was prominent impairment of memory, attention, information-processing speed, and executive functioning, and mild impairment in visuospatial function. This is in agreement with the results of Mai et al. [14], Elwan et al. [15], and Abraham and Rege [16].

ERP is a sensitive tool for examining arousal, attention, and vigilance. This study showed longer latencies and lower amplitudes of ERP p300 in MS patients than in controls. These results are in agreement with those of Whelan et al. [17]. In contrast, Gonzalez-Rosa et al. [18] reported that the amplitude of ERP is not affected in MS patients. This difference may be due to the inclusion of more patients with RRMS and those with lower physical disability.

In this study, there were decreases in the NAA/Cr and NAA/Cho ratios and increases in the Cho/Cr ratio in MS patients in comparison with the control group. This is in agreement with Sajja et al. [5].

The results of this study showed that patients with more severe physical disabilities had more cognitive dysfunctions, more prolonged latencies, and lower amplitudes of ERPs p300 as well as more MRS changes. This is in agreement with the results of Kocer et al. [19].

The study showed that ERP p300 and MRS changes are more severe in patients with more CI. This is in agreement with the findings of Kocer et al. [19].

The study showed that CI is more pronounced in SPMS patients than in those with PPMS and RRMS. This is in agreement with the results of Falini et al. [20] and Ruet et al. [21], the former of which can be attributed to more physical disabilities, older age, and longer disease duration in the study group.

Conclusion

Impaired cognitive functions are common MS manifestations occurring early in the disease course and occur more frequently in SPMS patients than in PPMS and RRMS patients. The most commonly affected cognitive domains are memory, attention, information-processing speed, and executive functions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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