Primary Angiitis of the Central Nervous System in Adults: A Comprehensive Review of 76 Biopsy-Proven Case Reports

Figures & data

Figure 1 Study population flowchart.

Table 1 Baseline Characteristics of 76 PACNS Patients Confirmed by Histopathology

Parameters	All (N=76)	Lymphocytic (N=49)	Granulomatous (N=13)	ABRA (N=11)	Necrotizing (N=3)	Cases
Basic Information
Male, n(%)	44(57.9)	26(53.1)	11(84.6)	7(63.6)	0(0)	76
Age, years	47.0(35.0–57.0)	46.0(34.0–52.0)	35.0(28.0–48.0)	72(58.0–76.0)	/	76
Neurological symptoms, n(%)
Focal symptoms	60(78.9)	41(83.7)	10(76.9)	7(63.6)	2(66.7)	76
Seizures	23(30.3)	16(32.7)	2(15.4)	3(27.3)	2(66.7)	76
Headache	41(52.6)	25(51.0)	8(61.5)	5(45.5)	2(66.7)	76
Cognition	29(38.2)	9(18.4)	7(53.8)	11(100)	2(66.7)	76
CSF parameters, n(%)
Elevated WBC	33(55.9)	19(51.4)	8(80.0)	5(55.6)	1(33.3)	59
Elevated Protein	45(76.3)	28(75.7)	9(90.0)	6(66.7)	2(66.7)	59
Imaging, n(%)
Spinal cord involvement	11(14.5)	7(14.3)	3(23.1)	0(0)	1(33.3)	76
Vascular stenosis	15(28.8)	11(30.6)	2(28.6)	1(16.7)	1(33.3)	52
Mass effect	47(61.8)	29(59.2)	6(46.2)	10(90.9)	2(66.7)	76
Enhancement	60(92.3)	38(90.5)	11(91.7)	8(100)	3(100)	65
Biopsy
Time window, months*	1.1(0.3–6.8)	0.5(0.3–5.0)	5.0(0.9–24.0)	2.0(0.3–7.0)	/	76
Number=2, n(%)	8(10.5)	4(8.2)	1(7.7)	1(9.1)	2(66.7)	76
Antibody
CD3/4/8	22 (68.8)	17(70.8)	2(50.0)	3(75.0)	/	32
CD20	11 (34.4)	11(45.8)	0(0)	0(0)	/	32
CD68	16 (50.0)	10(41.7)	2(50.0)	4(100.0)	/	32
Treatment, n(%)
Hormone	69(90.8)	43(87.8)	12(93.3)	11(100.0)	3(100.0)	76
Immunotherapy	54(71.1)	34(69.4)	11(84.6)	7(63.6)	2(66.7)	76
Number of drugs	2(1–3)	2(1–2)	2(1–3)	2(1–2)	/	76
Follow-up
Time, months	17.3(6.3–32.4)	15.0(6.0–29.3)	33.0(8.0–60.0)	10.8(8.0–24.0)	/	76
Recurrent events, n(%)	41(53.9)	23(46.9)	8(61.5)	7(63.6)	3(100.0)	76

Abbreviations: PACNS, primary angiitis of the adult central nervous system; ABRA, Aβ-related angiitis; CSF, cerebrospinal fluid; WBC, white blood cell; CD3/4/8, T lymphocytes antigen CD3/4/8; CD20, B-lymphocyte antigen CD20; CD68, macrophage antigen CD68.

Table 2 Baseline Characteristics of 7 Therapeutic Drugs

Parameters (N=76)	GC (N=69)	CYC (N=48)	AZA (N=9)	RTX (N=8)	MMF (N=8)	MTX (N=4)	IVIG (N=3)
Basic Information
Male, n(%)	39(56.5)	31(64.6)	6(66.7)	6(75.0)	5(62.5)	1(25.5)	3(100.0)
Age, years	47.0(35.0–57.0)	50.0(39.0–56.8)	39.0(25.0–53.0)	34.0(29.5–41.5)	32.5(22.3–47.3)	50.0(47.8–59.0)	/
Neurological symptoms, n(%)
Focal symptoms	56(81.2)	38(79.2)	7(77.8)	7(87.5)	7(87.5)	4(100.0)	3(100.0)
Seizures	19(27.5)	15(31.3)	4(44.4)	3(37.5)	4(50.0)	1(25.0)	1(33.3)
Headache	37(53.6)	26(54.2)	5(55.6)	2(25.0)	5(62.5)	2(50.0)	1(33.3)
Cognition	28(40.6)	20(41.7)	4(44.4)	1(12.5)	2(25.0)	1(25.0)	3(100.0)
CSF parameters, n(%)
Elevated WBC	31(57.4)	23(62.2)	5(71.4)	2(40.0)	4(57.1)	3(100.0)	2(66.7)
Elevated Protein	42(77.8)	31(83.8)	6(85.7)	4(80.0)	7(100.0)	2(66.7)	3(100.0)
Imaging, n(%)
Involvement Spinal cord	11(15.9)	10(20.8)	3(33.3)	1(12.5)	2(25.0)	0(0)	0(0)
Vascular stenosis	14(29.8)	9(27.3)	1(16.7)	2(50.0)	3(42.9)	1(33.3)	0(0)
Mass effect	43(62.3)	26(54.2)	5(55.6)	5(62.5)	4(50.0)	3(75.0)	(0)
Enhancement	54(93.1)	34(89.5)	6(100)	6(85.7)	7(100.0)	2(66.7)	2(100.0)
Biopsy
Time window, months	1.3(0.3–7.0)	3.0(0.3–8.0)	1.0(0.3–9.0)	3.0(0.3–5.0)	2.5(0.3–20.0)	3.8(0.3–10.8)	/
Number=2, n(%)	7(10.1)	5(10.4)	1(11.1)	8(11.6)	0(0)	0(0)	0(0)
Antibody
CD3/4/8	20(71.4)	12(70.6)	4(80.0)	3(100.0)	1(33.3)	2(100.0)	1(50.0)
CD20	9(32.1)	5(29.4)	2(40.0)	3(100.0)	0(0)	0(0)	0(0)
CD68	14(50.0)	10(58.8)	3(60.0)	1(33.3)	2(66.7)	0(0)	1(50.0)
Follow-up
Time, months	19.0(6.5–34.5)	23.3(9.0–39.8)	28.0(21.5–60.0)	19.0(9.8–27.0)	45.0(10.9–72.6)	20.3(10.9–28.9)	/
Recurrence frequency	37(53.6)	27(56.3)	6(66.7)	7(87.5)	8(100.0)	2(50.0)	2(66.7)

Abbreviations: CSF, cerebrospinal fluid; WBC, white blood cell; CD3/4/8, T lymphocytes antigen CD3/4/8; CD20, B-lymphocyte antigen CD20; CD68, macrophage antigen CD68; GC, glucocorticoid; CTX, cyclophosphamide; AZA, azathioprine; RTX, rituximab; MMF, mycophenolate mofetil; MTX, methotrexate; IVIG, gamma globulins.

Figure 2 Combination of different treatment options in a no-recurrent population.

Abbreviations: GC, glucocorticoid; CTX, cyclophosphamide; AZA, azathioprine; RTX, rituximab; MMF, mycophenolate mofetil; MTX, methotrexate; IVIG, gamma globulins; Eta, etanercept.

Figure 3 Combination of different treatment regimens in populations with relapses and deaths. The red star represents a relapse.

Abbreviations: GC, glucocorticoid; CTX, cyclophosphamide; AZA, azathioprine; RTX, rituximab; MMF, mycophenolate mofetil; MTX, methotrexate; IVIG, gamma globulins; Eta, etanercept.

Table 3 Characteristics of Patients with Recurrent Events and Death Outcomes

Parameters (N=76)	Relapse Events		p-value	Death		p-value
	No (N=35)	Yes (N=41)		No (N=68)	Yes (N=8)
Basic Information
Male, n(%)	18(51.4)	26(63.4)	0.291	40(68.8)	4(50.0)	0.921
Age, years	47.0(35.0–57.0)	47.(31.0–60.0)	0.827	46.0(33.5–57.0)	52.0(38.0–63.5)	0.477
Neurological symptoms, n(%)
Focal symptoms	27(77.1)	33(80.5)	0.721	53(77.9)	7(87.5)	0.866
Seizures	5(14.3)	18(43.9)	0.005	20(29.4)	3(37.5)	0.949
Headache	17(48.6)	23(56.1)	0.512	35(51.5)	5(62.5)	0.828
Cognition	11(31.4)	18(43.8)	0.265	26(38.2)	3(37.5)	1.000
CSF parameters, n(%)
Elevated WBC	12(50.0)	21(60.0)	0.447	27(51.9)	6(85.7)	0.199
Elevated Protein	16(66.7)	29(82.9)	0.151	39(75.0)	6(85.7)	0.879
Imaging, n(%)
Involvement Spinal cord	3(8.6)	8(19.5)	0.177	9 (13.2)	2 (25.0)	0.716
Vascular stenosis	7(31.8)	8(26.7)	0.685	13(27.7)	2(40.0)	0.952
Mass effect	23(65.7)	24(58.5)	0.521	43(63.2)	4(50.0)	0.731
Enhancement	26(83.9)	34(100.0)	0.049	53(91.4)	7(100.0)	0.954
Biopsy
Time window, months	0.5(0.3–4.0)	4.0(0.5–9.5)	0.003	1.4(0.3–7.0)	0.8(0.3–5.8)	0.493
Number=2, n(%)	2(5.7)	6(14.6)	0.207	5 (7.4)	3 (37.5)	0.043
ABRA	4(11.4)	7(17.1)	0.486	11(47.8)	0(0)	1.000
Antibody
CD3/4/8	11(64.7)	11(73.3)	0.886	9 (29.0)	1(100.0)	0.681
CD20	3(17.6)	8(53.3)	0.034	20 (64.5)	1 (100.0)	1.000
CD68	6(35.3)	10(66.7)	0.077	16 (51.6)	0 (0)	1.000
Treatment, n(%)
Immunotherapy	23(65.7)	31(75.6)	0.343	52(76.5)	2(25.0)	0.009
Follow-up
Time, months	8.0(4.5–30.5)	19.0(9.5–34.5)	0.079	19.0(6.9–36.0)	3.3(0.6–17.6)	0.012

Abbreviations: ABR, Aβ-related angiitis; CSF, cerebrospinal fluid; WBC, white blood cell; CD3/4/8, T lymphocytes antigen CD3/4/8; CD20, B-lymphocyte antigen CD20; CD68, macrophage antigen CD68.