Central nervous system manifestations of tuberous sclerosis complex: A single centre experience in Qatar

Munira Aden; Mahmoud O. Fawzi; Debra Prosser; Muhammad Ather; Mehak Raja; Moegamad A. Ederies; Khalid Al-Kharazi; Ata U. Maaz

doi:10.15537/smj.2024.45.11.20240444

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Table 1

- Patients and disease characteristics (N=38).

Characteristics	n (%)
Gender
Male	19 (50.0)
Female	19 (50.0)
Age at diagnosis, median (range)	4 (0-72)
Age group
Up to 4 months	20 (52.6)
4-12 months	14 (36.8)
Over 12 months	4 (10.5)
Diagnosis
Qatar	24 (63.1)
Elsewhere	14 (36.9)
Family history
Yes	10 (26.3)
No	28 (73.7)
Genetic analysis
Mutation in TSC1	1 (2.6)
Mutation in TSC2	33 (86.8)
Genetic studies negative	4 (10.5)
Presentation
Infantile spasms	14 (36.8)
Seizures (other than infantile spasms)	18 (47.3)
Developmental delay	5 (13.1)
Cardiac rhabdomyoma	8 (21.0)
Hypopigmented spots	5 (13.1)
Major criteria for TSC
Hypomelanotic nodules	29 (76.3)
Angiofibroma	20 (52.6)
Ungual fibroma	0 (0.0))
Shagreen patch	7 (18.4)
Retinal hamartoma	5 (13.1)
Cortical dysplasia	29 (76.3)
Subependymal nodules	37 (97.3)
SEGA	10 (26.3)
Cardiac rhabdomyoma	16 (42.1)
LAM	0 (0.0)
AML	22 (57.8)
Minor criteria for TSC
Confetti lesions	4 (10.5)
Dental enamel pits	2 (5.3)
Intra-oral fibroma	2 (5.3)
Retinal achromic patch	0 (0.0)
Multiple renal cysts	29 (76.3)
Non-renal hamartomas	4 (10.5)
Neuro-imaging features
Tubers	37 (97.3)
SEN	37 (97.3)
SEGA	10 (26.3)

Values are presented as numbers and percentages (%).

TSC: tuberous sclerosis complex, SEGA: subependymal giant cell astrocytoma, LAM: lymphangioleiomyomatosis, AML: angiomyolipoma, SEN: subependymal nodules

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Table 2

- Presenting clinical and radiological features for all patients with tuberous sclerosis.

No.	Gender	Age at diagnosis (months)	Presentation	FH	Genetics	Epilepsy (E-CHESS score)	DD	LD	Tubers (dominant lobe)	Mineral-ization	SEN	SEGA
1.	M	1	Fits, RM	No	TSC2	Yes (7)	Yes	Yes	Yes (right temporal lobe)	Partial	Foramen of Monro (b/l)	Yes
2.	M	6	Fits	No	TSC2	Yes (8)	Yes	Yes	Yes (right Frontotemporal lobe)	No	Foramen of Monro (L)	Yes
3.	F	6	Fits, DD	No	TSC2	Yes (7)	Yes	Yes	Yes (none)	No	Frontal horn (R)	Yes
4.	F	4	IS, HS	No	TSC2	Yes (8)	Yes	Yes	Yes (both frontal lobes)	No	Foramen of Monro (b/l)	No
5.	M	3	Fits, LD	No	TSC2	Yes (7)	Yes	Yes	Yes (none)	Partial	Frontal horn (R)	Yes
6.	F	0		No	TSC2	No	No	No	Yes (both frontal lobes)	No	Foramen of Monro (R)	Yes
7.	M	11	IS	No	TSC2	Yes (11)	Yes	No	Yes (left temporoparietal lobes)	No	Lateral ventricles (b/l)	No
8.	M	0	IS	No	TSC2	No	No	No	Yes (none)	No	Foramen of Monro (R)	No
9.	M	1	RM	Yes	TSC2	Yes (7)	Yes	Yes	Yes (right Parieto-occipital lobe)	Partial	Foramen of Monro (L)	No
10.	M	7	IS	Yes	TSC2	Yes (8)	Yes	Yes	Yes (none)	Partial	Foramen of Monro (b/l)	No
11.	F	12	HS	Yes	TSC2	No	No	Yes	Yes (none)	No	Frontal horn (R)	No
12.	F	1	Fits	Yes	TSC2	Yes (8)	Yes	Yes	Yes (none)	Partial	Frontal horn (left)	No
13.	M	6	IIS	Yes	TSC2	Yes (9)	No	Yes	Yes (none)	Partial	Lateral ventricles (b/l)	No
14.	M	2	Fits	Yes	TSC2	Yes (8)	Yes	Yes	Yes (none)	Partial	Lateral ventricles (b/l)	No
15.	M	10	IS	No	TSC2	Yes (10)	Yes	Yes	Yes (none)	Partial	Foramen of Monro (L)	No
16.	M	2	IS	No	TSC2	Yes (8)	Yes	Yes	Yes (left frontal lobe)	Partial	Lateral ventricles (b/l)	No
17.	F	12	Fits	No	TSC2	Yes (8)	Yes	Yes	Yes (none)	No	Foramen of Monro (b/l)	Yes
18.	M	4	Fits	No	TSC2	Yes (8)	Yes	Yes	Yes (none)	No	Foramen of Monro (b/l)	Yes
19.	F	9	DD, RM, IS	No	TSC2	Yes (11)	Yes	Yes	Yes (left temporal lobe)	Partial	Lateral ventricles (b/l)	No
20.	F	1	HS, RM, IS	No	TSC2	No	No	No	Yes (none)	Partial	Lateral ventricles (b/l)	No
21.	F	2	IS, RM	No	TSC2	Yes (8)	Yes	Yes	Yes (none)	No	Foramen of Monro (L)	Yes
22.	M	72	Fits	No	TSC2	Yes (9)	No	No	Yes (left temporal lobe)	Partial	Foramen of Monro (L)	Yes
23.	F	2	IS	No	TSC2	Yes (8)	Yes	Yes	Yes (none)	No	Foramen of Monro (b/l)	No
24.	F	24	Fits	No	TSC2	Yes (6)	Yes	Yes	Yes (left frontal lobe)	Partial	Frontal horn (L)	No
25.	M	1	RM, LD	Yes	TSC2	No	Yes	Yes	Yes (all left sided lobes)	Partial	Lateral ventricles (b/l)	No
26.	F	2	IS, DD	No	TSC2	Yes (9)	Yes	Yes	Yes (none)	No	Frontal horn (R)	Yes
27.	M	4	Fits	No	TSC2	No	Yes	Yes	Yes (none)	Partial	Foramen of Monro (R)	Yes
28.	F	11	Fits	Yes	TSC2	Yes (6)	Yes	Yes	Yes (none)	No	Lateral ventricles(B/l)	No
29.	F	2	RM, HS	No	TSC2	Yes (9)	No	No	Yes (none)	No	None	No
30.	F	9	Fits	No	TSC2	Yes (7)	No	No	Yes (none)	No	Frontal horn (R)	Yes
31.	M	3	Fits	No	TSC2	Yes (8)	No	No	Yes (none)		Lateral ventricles (b/l)	No
32.	F	12	Fits, LD	Yes	None	Yes (9)	No	Yes	Yes (left parietal lobe)	Partial	Lateral ventricles (b/l)	No
33.	M	36	Fits	Yes	None	No	No	No	Yes (none)	No	Foramen of Monro (b/l)	No
34.	M	0	HS	No	TSC2	No	No	No	Yes (none)	Partial	Foramen of Monro (b/l)	Yes
35.	M	36	DD	No	None	No	No	Yes	Yes (right frontal lobe)	Partial	Foramen of Monro (b/l)	No
36.	F	9	Fits	No	TSC 1	Yes (5)	No	No	Yes (both frontal lobes)	No	None	No
37.	F	2	RM, IS	No	TSC2	Yes (8)	No	No	Yes (left frontal lobe)	No	Lateral ventricles (b/l)	No
38.	F	8	Fits	No	None	Yes (8)	Yes	Yes	Yes (left frontal and right occipital lobes)	Partial	Foramen of Monro (R)	No

DD: developmental delay, LD: learning disabilities, E-CHESS: early childhood epilepsy severity score, SEN: subependymal nodules, SEGA: subependymal giant cell astrocytoma, b/l: bilateral, M: male, F: female, RM: rhabdomyoma, IS: infantile spasm, HS: hypopigmented spots, FM: Foramen of Monro, LV: lateral ventricle, FH: frontal horn, L: left, R: right

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Table 3

- Frequency of tuberous sclerosis associated neuropsychiatric disorders features among tuberous sclerosis patients (n=29).

TAND features	Present	Absent	Percentages (%)
Temper tantrum	5	24	17.24%
Aggressive outbursts	8	21	27.59%
Anxiety	1	28	3.45%
Depressed mood	8	21	27.59%
Self-injury	1	28	3.45%
Difficulties paying attention	18	11	62.07%
Overactivity/hyperactivity	11	18	37.93%
Impulsivity	8	21	27.59%
Absent or delayed onset of language to communicate	21	8	72.41%
Poor eye contact	13	16	44.83%
Repetitive behaviours	3	26	10.34%
Sleep difficulties	4	25	13.79%
Difficulties with eating	5	24	17.24%
Extreme shyness	1	28	3.45%
Mood swings	11	18	37.93%
Repeating words or phrases over and over again	2	27	6.90%
Difficulties getting on with peers	11	18	37.93%
Very rigid or inflexible about how to do things	7	22	24.14%
Restlessness or fidgetiness	1	28	3.45%
ASD	12	16	42.86%
ADHD	7	22	24.14%
Intellectual disability	20	9	68.97%
Reading	19	10	65.52%
Writing	20	9	68.97%
Spelling	20	9	68.97%
Mathematics	19	10	65.52%
Multitasking	12	17	41.38%
Memory	15	14	51.72%
Visuo-spatial tasks	11	18	37.93%
Cognitive flexibility	10	19	34.48%
Low self-esteem of the patient	1	28	3.45%
Family stress	9	20	31.03%
Relational difficulties of the patient	6	23	20.69%

Values are presented as numbers and percentages (%).

TAND: tuberous sclerosis complex associated neuropsychiatric disorders, ASD: autistic spectrum disorder, ADHD: attention deficit hyperactivity disorder

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Table 4

- Severity of epilepsy and response to therapy using the “early childhood epilepsy severity score” (N=30).

Seizure characteristics	n (%)
Frequency^{^*}
No seizures	10 (33.3)
Weekly	14 (46.6)
Daily	6 (20.0)
More than daily	0 (0.0)
Time period
Less than one month	8 (26.6)
1-6 months	6 (20.0)
More than 6 months	16 (53.3)
No of seizure types^{^*}
1	25 (83.3)
2	4 (13.3)
3	1 (3.3)
Anticonvulsants
None	3 (10.0)
1-2	15 (50.0)
3	12 (40.0)
Response to treatment
Complete cessation	19 (63.3)
Partial cessation	8 (26.6)
No response	3 (10.0)
E-CHESS score
2-7	9 (30.0)
More than 7	21 (70.0)

Values are presented as numbers and percentages (%).

E-CHESS: early childhood epilepsy severity score

↵* Seizure types: infantile spasms: 14, tonic/clonic:12, absence: 5, atonic: 3, tonic: 3, focal: 3, myoclonic:2, behaviour arrest: 2, and no epilepsy: 8.