Neuropsychiatric symptoms and their impact on quality of life among patients with multiple sclerosis

Abstract

Background:

Neuropsychiatric symptoms in multiple sclerosis (MS) are common, often unrecognized. These symptoms often increase morbidity and lead to poor quality of life (QOL).

Aim:

Aim of the study was to assess the presence and severity of neuropsychiatric morbidity and the extent to which they impair QOL in patients with MS.

Methods:

In a cross-sectional study conducted at a South Indian tertiary center, 52 MS patients were assessed using the Neuropsychiatric Interview, Pathological Laughter and Crying Scale, Diagnostic Criteria for Psychosomatic Research and MSQOL-54.

Results:

We found that, overall, 61.54% of patients had neuropsychiatric symptoms, primarily irritability (48.1%), depression (28.8%), sleep disturbances (19.2%), elation (13.5%), pathological laughter and crying (11.5%), appetite disturbances (11.5%), and agitation (7.7%). QOL was significantly impaired in patients with neuropsychiatric symptoms compared to those without.

Conclusion:

It appears that neuropsychiatric symptoms and associated impaired QOL are common in MS and persist irrespective of disease factors like stage, progression, and treatment. Hence, early screening and intervention are warranted.

INTRODUCTION

Multiple sclerosis (MS) is a common demyelinating disease with a worldwide incidence of 5.2/100,000 person-years.[1] In India, the prevalence of MS has increased from 1.33/100,000 to 8.35 in the last 30 years, with mean age at onset 21.1 years, and female-to-male ratio 3.6:1.[2] Neuropsychiatric symptoms (NPS) affect ~60% MS patients and are often underdiagnosed and untreated. Medications for MS can also cause these symptoms, and NPS pose a substantial burden on patients with MS.[3]

NPS in MS present as affective and behavioral changes.[4] Major depressive disorder is the most common psychiatric illness in MS (prevalence ~30%), followed by anxiety disorder.[5] Non-specific NPS are frequent; a study using neuropsychiatric inventory (NPI) reported 80% of patients had at least one symptom, with most frequent being depressive symptoms, sleep disturbance, irritability/emotional lability, apathy, and euphoria.[6]

Indian studies focus mainly on depression and anxiety and less on other NPS.[7,8] Comorbid NPS can reduce quality of life (QOL), increase patient and caregiver burden. The current study aimed to assess NPS in MS and its association with MS-related QOL.

METHODS

The study was conducted between July 1, 2019, to July 31, 2020 at a tertiary care neuropsychiatric hospital using a consecutive sampling technique with a cross-sectional design. The study was approved by the Institutional Ethics Review Board and written informed consent was obtained from the participants. We included patients aged ≥18 years fulfilling the McDonald’s criteria[9] for MS with clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS), and with Hindi mental state examination (HMSE)[10] score ≥24. We excluded patients diagnosed with other types of MS such as radiologically isolated syndrome (RIS), primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS), and MS with comorbid autoimmune encephalitis.

Assessment tools

A semi-structured schedule was used to collect socio-demographic and clinical details such as age, gender, address, education, occupation, marital status, family status, socio-economic status, age at onset of MS, duration of illness and treatment details. The following structured instruments were administered:

1. The Neuropsychiatric Inventory Questionnaire (NPI-Q)[11] is a self-administered questionnaire with 12 symptom domains, each with yes/no response questions and a severity rating (1-mild, 2-moderate, and 3-severe).

2. Pathological laughter and crying scale (PLACS): Interviewer-rated scale to assess pathological laughter and crying. There are eight items each for laughter and crying, all items scored 0–3, with maximum score of 48. A score of ≥13 is considered positive for pathological laughter and crying.[12]

3. Diagnostic criteria for psychosomatic research (DCPR): An interviewer-rated scale to assess psychological distress secondary to medical illness. There are 12 items, each with a yes/no response.[13]

4. Expanded disability status scale (EDSS): It ranges from 0 to 10, with 0.5 increments indicating worsening levels of disability, mainly measured using walking as an indicator.[14]

5. Multiple sclerosis quality of life-54 (MSQOL-54): It combines a generic QOL scale with MS-specific items in the form of a structured self-report or interviewer-administered questionnaire. The result is expressed as two summary scores—physical health and mental health.[15]

Statistical Analysis: Data were analyzed using SPSS-21.[16] The Kolmogorov-Smirnov test assessed normality. Socio-demographic and clinical variables (e.g., MS type, treatment, NPS) are described using frequency and percentage. Mean, standard deviation (SD) is used for normally distributed data, and Median, interquartile range (IQR) are used for asymmetrically distributed data. For comparative analysis between groups (with/without NPS), Chi-square and Fischer’s exact tests are used. For numerical variables, the independent sample t-test (normally distributed) with Cohen’s d and Mann-Whitney-U test (asymmetrically distributed) with rank-biserial correlation are used.

RESULTS

Socio-demographic profile

We assessed 52 MS patients: 36 (69%) were women, 41 (78.8%) were educated up to graduation, 40 (76.9%) were employed, 26 (50%) were married, 34 (65.4%) lived in a nuclear family, and 38 (73.1%) belonged to the middle socio-economic status.

Clinical details

The mean age at onset of MS was 25.81 years (SD = 9). Of 52 patients, 41 (78.8%) had RRMS; the rest had CIS. Median illness duration was 42 months (IQR = 67.5), median episode duration was 25 days (IQR = 50), and median episodes numbered three (IQR = 2). Disease-modifying agents (DMAs) were used by 32 (61.5%) patients, with the majority being on beta-interferon (15, 28.8%), azathioprine (10, 19.2%), dimethyl fumarate (DMF), rituximab (5, 9.6% each), mycophenolate mofetil (MMF) (3, 5.7%), teriflunomide (2, 3.8%), and glatiramer acetate (1, 1.9%).

Neuropsychiatric symptoms in multiple sclerosis

We defined the presence of NPS as meeting criteria for at least one symptom across the NPI, PLACS, or DCPR. We report the proportion of patients with any NPS—as the majority experienced multiple symptoms, these proportions are not mutually exclusive. “Irritability” on NPI and “Irritable Mood” on DCPR overlap and were marked positive on both scales. All patients who had irritability or irritable mood invariably were also positive for other NPS. In total, 32 of 52 (61.5%) patients had at least one NPS; 30 had more than one [Table 1]. Of the patients with single NPS, one reported demoralization and another reported Type-A behavior on the DCPR. Age at onset and MS duration did not differ between individuals with and without psychiatric morbidity. Comparison between RRMS and CIS groups was not done (78.8% had RRMS). A correlation with DMA use was not attempted, as only four patients on DMAs had psychiatric morbidity.

Table 1.

Neuropsychiatric symptoms in the study population

Scale used	Neuropsychiatric symptom	Proportion* [n, %] (n=52)
Neuropsychiatric Inventory	Agitation/aggression	4, 7.7%
	Depression/dysphoria	15, 28.8%
	Anxiety	7, 13.5%
	Irritability/lability	25, 48.1%
	Motor disturbance	2, 3.8%
	Elation/euphoria	7, 13.5%
	Night time behaviors	10, 19.2%
	Appetite/eating	6, 11.5%
Diagnostic Criteria for Psychosomatic Research	Illness denial	3, 5.8%
	Type A behavior	10, 19.2%
	Irritable mood	25, 48.1%
	Demoralization	10, 19.2%
Pathological Laughter and Crying Scale	Pathological laughter	1, 1.9%
	Pathological crying	5, 9.5%

*Proportions are not mutually exclusive. Proportion represented as n, %

Quality of life and neuropsychiatric symptoms

Table 2 compares QOL between patients with and without psychiatric symptoms. Those with NPS (at least one NPS in any scale used) had statistically significantly lower scores in overall QOL, physical health composite, mental health composite, health perception, energy/fatigue, health distress, emotional wellbeing, emotional role limitation, cognitive function, sexual, and social function. No significant differences were found in physical function, physical role limitation, or pain. Due to a sample size imbalance (n = 2 with single NPS versus n = 30 with multiple NPS), we did not compare single vs overlapping symptoms.

Table 2.

Comparison of quality of life in patients with and without neuropsychiatric symptoms

MSQOL-54 subscales	Neuropsychiatric symptoms				t	P	Effect size
	Present (n=32)	Absent (n=20)	Present (n=32)	Absent (n=20)
	Mean (Standard Deviation)		Standard error of mean				Cohen’s d (95% CI)
Overall QOL*	56.2 (22.3)	75 (14.1)	3.947	3.174	−3.172	0.001	−0.95 (−1.55, −0.37)
Energy-fatigue*	52.8 (17.5)	67.8 (13.2)	3.109	2.951	−3.5	0.002	−0.94 (−1.52, −0.35)
Health perceptions*	37.9 (27.2)	61.2 (21.5)	4.814	4.824	−3.419	0.002	−0.93 (−1.51, −0.34)
Physical health composite score*	55.7 (20.2)	75.9 (16.6)	3.581	3.726	−3.909	<0.001	−1.06 (−1.66, −0.47)
	Mean rank		Sum of ranks		U	P	r-statistic$ (95% CI)
Health distress#	20.81	35.6	666	712	138	0.001	−0.57 (−0.89, −0.24)
Emotional wellbeing#	20.66	35.85	661	717	133	<0.001	−0.58 (−0.91, −0.26)
Role limitation-emotional#	23.75	30.9	760	618	232	0.029	−0.27 (−0.60, 0.05)
Cognitive function#	22.08	33.58	706.5	671.5	178.5	0.003	−0.44 (−0.77, −0.12)
Mental health composite score#	19.69	37.4	630	748	102	<0.001	−0.68 (−1.00, −0.35)
Physical function#	24.31	30.0	778	600	250	0.183	−0.22 (−0.54, 0.11)
Role limitation-physical#	24.09	30.35	763.5	614.5	235.5	0.084	−0.26 (−0.59, 0.06)
Sexual function#	21.3	34.83	681.5	696.5	153.5	<0.001	−0.52 (−0.84, −0.19)
Social function#	21.92	33.83	701.5	676.5	173.5	0.005	−0.46 (−0.78, −0.13)
Pain#	23.86	30.73	763.5	614.5	235.5	0.084	−0.26 (−0.59, 0.06)

*Independent sample t-test used for variables with normal distribution; ^#Mann-Whitney U test used for variables without normal distribution; ^$Rank biserial correlation. P < 0.05 considered as significant. MSQOL=Multiple Sclerosis Quality of Life-54; SD=Standard deviation; CI=Confidence Intervals

Patients with NPS showed low QOL with large effect sizes (Cohen’s d >0.9) in overall QOL, energy-fatigue, health perceptions, and physical health. Rank biserial correlations also revealed large effects (r > 0.5) for health distress, emotional wellbeing, mental health, and sexual function, alongside medium effects (r > 0.2) for cognitive and social subscales [Table 2]. While these findings indicate a substantial link between NPS and reduced QOL, interpretation must be cautions due to the small sample size (N = 52).

DISCUSSION

The current study found that almost a third of the study population (61.5%) had at least one NPS and was associated with impaired QOL. This high NPS morbidity is consistent with previous studies.[6] In India, documented mean age at onset of MS is 38.3 years.[17] The younger age at onset in our sample may reflect selection bias, as we recruited from a university teaching hospital treating difficult/unusual manifestations of MS. Consistent with studies in Asian population,[2] our sample had female preponderance.

Irritability was seen in nearly one-third of our MS patients, particularly those with younger age at onset. This symptom has not been systematically assessed among Indian patients. Irritability can be independent or part of depression, mania, or mixed-affective states. One study reported that MS patients scored higher on irritability than those with other chronic medical conditions.[6] Sleep disturbance, the third most common symptom in our MS patients, is four times more common in MS than general population and significantly affects QOL.[18] A previous Indian study reported 52% prevalence of sleep disturbance in MS.[7] Similarly, our findings of high depressive and anxiety symptoms align with prior research in the Indian population.[8] The prevalence of pathological crying (9.5%) and pathological laughter (1.9%) were also similar to a previous study.[4] QOL was impaired in most domains for MS patients with comorbid NPS. This aligns with other studies where depression, disability level, and fatigue were independent predictors of QOL in MS.[19] Thoroughly evaluating and managing NPS is essential in MS. However, diagnosis is often complex, as symptoms like fatigue, sleep disturbances, and appetite loss overlap between psychiatric disorders and MS itself. Effectively treating depression and other NPS not only enhances QOL, but also improves MS clinical outcomes.[20] Consequently, patients with MS require routine NPS screening and streamlined access to mental health care.

This study focused on NPS and their effect on QOL, rather than only diagnosable psychiatric morbidity. It specifically includes irritability as a symptom domain, therefore adding to existing literature. However, the study has limitations: The small sample size from a single tertiary center limited generalizability, and cross-sectional design prevented assessing longitudinal interactions between NPS and MS. Additionally, we did not analyze the impact of psychiatric treatment on NPS or QOL. While excluding progressive MS ensured homogeneity for the RRMS group, it likely omitted patients with higher NPS burden. Finally, the lack of neuroimaging data prevented correlating these clinical findings with specific brain regions.

CONCLUSIONS

Neuropsychiatric morbidity in MS is often under-detected and under-treated, despite high prevalence and available effective treatments. NPS adversely affect functional status, causing increased time lost from work, job changes, interpersonal issues, reduced social support, decreased treatment adherence and poor QOL, often disproportionate to the neurological symptoms alone. It is therefore essential to have a multi-pronged, team-based approach (including a neurologist, psychiatrist, counsellor) for early, systematic assessment and adequate treatment of psychiatric morbidity, thereby improving QOL. Future, larger-cohort studies should prospectively assess symptom domains and their impact on disability, QOL, and neuropsychiatric changes in both RRMS and progressive MS.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.