Long-term neurological and neurocognitive impairments after tick-borne encephalitis in Lithuania - a prospective study

Figures & data

Table 1. Distribution of demographics and clinical features between patients and healthy controls.

Demographic data/ Clinical features	TBE patients (full cohort) N = 98	TBE patients (follow-up 1) N = 77	TBE patients (follow-up 2) N = 61	Healthy controls N = 77
Age (average (SD), years)	52.12 (16.62)	52.51 (15.62)	54.28 (15.55)	51.53 (15.56)
Age distribution (N, %)
18–30 Years	12 (12.2%)	7 (9.1%)	4 (6.6%)	7 (9.1%)
31–40 Years	12 (12.2%)	11 (14.3%)	8 (13.1%)	11 (14.3%)
41–50 Years	18 (18.4%)	13 (16.9%)	10 (16.4%)	13 (16.9%)
51–60 Years	25 (25.5%)	22 (28.6%)	17 (27.9%)	22 (28.6%)
61–70 Years	18 (18.4%)	14 (18.2%)	12 (19.7%)	14 (18.2%)
71–80 Years	11 (11.2%)	9 (11.7%)	9 (14.8%)	9 (11.7%)
81–90 Years	2 (2.0%)	1 (1.3%)	1 (1.6%)	1 (1.3%)
Gender distribution (N, %)
Male	59 (60.2%)	46 (59.7%)	36 (59.0%)	46 (59.7%)
Female	39 (39.8%)	31 (40.3%)	25 (41.0%)	31 (40.3%)
Education distribution (N, %)
High school/lower	38 (38.8%)	26 (33.8%)	20 (32.8%)	26 (33.8%)
Vocational/Higher	41 (41.8%)	37 (48.0%)	28 (45.9%)	37 (48.0%)
University/College	16 (16.3%)	14 (18.2%)	13 (21.3%)	14 (18.2%)
Unknown	3 (3.1%)
Disease severity (N, %)
Mild	52 (53.0%)	41 (53.2%)	31 (50.8%)	n/a
Moderate	38 (38.8%)	28 (36.4%)	22 (36.1%)	n/a
Severe	8 (8.2%)	8 (10.4%)	8 (13.1%)	n/a

Table 2. Neurological signs and subjective symptoms during the acute phase, discharge and both follow-ups.

a) Objective signs	Acute phase N = 98	Discharge N = 98	1^st Follow-up N = 77	2^nd Follow-up N = 61
	N (%)	N (%)	N (%)	N (%)
At least one neurological sign	87 (88.8)	45 (45.9)	28 (36.4)	24 (39.3)
Fever	98 (100.0)	0 (0.0)	0 (0.0)	0 (0.0)
Nausea/vomiting	60 (61.2)	0 (0.0)	0 (0.0)	0 (0.0)
Neck stiffness	32 (32.7)	0 (0.0)	0 (0.0)	0 (0.0)
Disturbance of consciousness	15 (15.3)	0 (0.0)	0 (0.0)	0 (0.0)
Tremor	38 (38.8)	22 (22.4)	18 (23.4)	18 (29.5)
Ataxia	50 (51.0)	22 (22.4)	9 (11.7)	6 (9.8)
Sensory disorders	7 (7.1)	1 (1.0)	8 (10.4)	6 (9.8)
Spinal nerve damage	12 (12.2)	12 (12.2)	8 (10.4)	7 (11.5)
Cranial nerve damage	12 (12.2)	8 (8.2)	5 (6.5)	4 (6.6)
N. oculomotorius	5 (5.1)	2 (2.0)	1 (1.3)	0 (0.0)
N. vestibulocochlearis	4 (4.1)	4 (4.1)	4 (5.2)	4 (6.6)
N. facialis	2 (2.0)	1 (1.0)	0 (0.0)	0 (0.0)
N. hypoglossus	1 (1.0)	1 (1.0)	0 (0.0)	0 (0.0)
Cerebellar syndrome	24 (24.5)	5 (5.1)	4 (5.2)	3 (4.9)
Dysphasia	7 (7.1)	4 (4.1)	2 (2.6)	1 (1.6)
Central paresis	0 (0.0)	0 (0.0)	2 (2.6)	2 (3.3)
Bulbar syndrome	1 (1.0)	1 (1.0)	1 (1.3)	1 (1.6)
Bladder dysfunction	2 (2.0)	2 (2.0)	1 (1.3)	2 (3.3)
Sexual dysfunction	–	–	3 (3.9)	3 (4.9)
b) Subjective symptoms	Acute phase N = 98	Discharge N = 98	1^st Follow-up N = 77	2^nd Follow-up N = 61
	N (%)	N (%)	N (%)	N (%)
At least one subjective symptom	98 (100.0)	60 (61.2)	56 (72.7)	41 (67.2)
Dysexecutive syndrome	16 (16.3)	3 (3.1)	0 (0.0)	0 (0.0)
Decreased memory	12 (12.2)	6 (6.1)	33 (42.9)	26 (42.6)
Increased irritability	–	–	28 (36.4)	18 (29.5)
Headache	93 (94.9)	26 (26.5)	28 (36.4)	18 (29.5)
Sleep disturbances	–	–	25 (32.5)	24 (39.3)
Decreased concentration	29 (29.6)	14 (14.3)	23 (29.9)	15 (24.6)
Decreased stress tolerance	–	–	19 (24.7)	11 (18.0)
Emotional instability	–	–	15 (19.5)	7 (11.5)
Behavior disorders	7 (7.1)	2 (2.0)	1 (1.3)	0 (0.0)

Figure 1. Rankin Scale (a) and Glasgow Outcome Scale (b) during discharge depending on disease severity.

Figure 2. Comparison of different cognitive domains between tick-borne encephalitis (TBE) patients and healthy controls depending on age, 6 months after TBE (*p < 0.05, **p < 0.01).

Figure 3. Comparison of different cognitive domains and Overall composite score between tick-borne encephalitis (TBE) patients and healthy controls depending on age, 6 months after TBE (*p < 0.05, **p < 0.01).

Table 3. Comparison of neurocognitive domains according to the severity of TBE at the time of first (6 months after the acute phase) follow-up controlling for age effect.

	Healthy controls		Mild TBE		Moderate/Severe TBE		Statistics
Cognitive domain	M	SE	M	SE	M	SE	F	p	Partial η^2
Speed of processing	46.62	1.45	43.48	2.02	40.42	2.23	2.87	0.06	0.04
Attention / vigilance	39.10	1.21	35.42	1.80	35.43	2.03	2.06	0.13	0.03
Working memory	42.35	1.07	38.83	1.50	43.46	1.65	2.59	0.08	0.03
Verbal learning	45.38	0.91	39.35	1.30	43.35	1.40	7.22	0.00	0.09
Visual learning	54.12	1.25	47.99	1.75	52.69	1.94	4.09	0.02	0.05
Reasoning and problem solving	48.38	0.94	47.38	1.32	47.00	1.46	0.39	0.68	0.01
Social cognition	58.36	1.37	58.37	2.04	57.96	2.22	0.01	0.99	0.00
Overall composite score	45.78	1.32	41.46	2.13	43.58	2.29	1.57	0.21	0.02

Selected results from ANOVA analysis. M-Estimated marginal mean. SE: standard error. Detailed analysis of between-subjects effects can be found in Supplementary Table 6.

Table 4. Changes in TBE patients’ neurocognitive functioning from 1^st to 2^nd follow-up. Paired sample t-test.

Cognitive domain		1^st Follow-up		2^nd Follow-up		Statistics
	N	M	SD	M	SD	t	df	Sig. (2-tailed)	Cohen’s d
Speed of processing	61	42.87	12.41	45.82	12.64	−4.38	60	0.00	−0.56
Attention / vigilance	49	37.29	8.60	40.12	10.70	−2.60	48	0.01	−0.37
Working memory	60	41.33	9.65	45.30	9.70	−4.27	59	0.00	−0.55
Verbal learning	60	41.25	7.71	45.80	8.82	−5.53	59	0.00	−0.71
Visual learning	60	50.57	10.71	57.85	9.42	−6.72	59	0.00	−0.87
Reasoning and problem solving	60	47.87	8.20	49.97	8.12	−2.79	59	0.01	−0.36
Social cognition	53	57.15	13.12	56.87	13.93	0.23	52	0.82	0.03
Overall composite score	45	43.58	11.94	49.58	11.91	−8.20	44	0.00	−1.22

Data availability statement

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.