FDG-PET shows weak correlation between focal motor weakness and brain metabolic alterations in ALS

Figures & data

Table 1 Patient characteristics, shown separately for those with a low versus high motor symptom burden.

	Total N = 131	Low symptom burden n = 66 (50.4%)	High symptom burden n = 65 (49.6%)
Age at the first FDG-PET scan, median (IQR)	63.0 (12.6)	62.3 (11.0)	63.8 (14.2)
Sex (male), n (%)	73 (55.3)	38 (56.7)	35 (53.8)
Family history of ALS, n (%)^a	9 (6.9)	8 (12.1)	1 (1.5)
Onset phenotype, n (%)^a
Lower extremity	41 (31.3)	18 (27.3)	23 (35.4)
Upper extremity	49 (37.4)	16 (23.3)	33 (50.7)
Bulbar	41 (31.3)	32 (48.5)	9 (13.8)
ALSFRS-R at the first FDG-PET scan, median (IQR)^a	40 (10)	43 (5)	35 (10)
Total motor symptom severity score at the first FDG-PET scan, median (IQR)^a	6 (5)	4 (2)	9 (4)
Time from first symptom to first FDG-PET scan, median days (IQR)^a	454 (552)	342 (309)	583 (748)

FDG-PET: fluorodeoxyglucose-positron emission tomography; IQR: interquartile range.

^aDifference between the two groups statistically significant, p < 0.05.

Table 2 Characteristics of 13 ALS patients with longitudinal FDG-PET imaging.

Patient number	Sex	Age at first scan	Onset area	Days from onset to first scan	Days from scan 1 to scan 2	FDG-PET alterations (yes/no)	Total motor symptom severity score
							Scan 1	Scan 2	Increase
1	F	52	Bulbar	224	344	Yes	7	18	11
2	M	64	UE, R	156	813	Yes	6	8	2
3	M	73	Bulbar	323	284	Yes	7	12	5
4	F	70	LE, R	3013	845	Yes	3	4	1
5	F	54	LE, L	636	1039	Yes	3	12	9
6	F	63	LE, R	474	470	Yes	6	9	3
7	M	24	UE, L	368	211	Yes	7	11	4
8	M	74	UE, L	349	429	Inconsistent	8	16	8
9	F	55	UE, L	500	499	No	2	9	7
10	F	60	LE, R	825	481	No	9	10	1
11	M	64	UE, R	380	596	No	2	6	4
12	F	57	UE, L	231	393	No	4	8	4
13	M	53	LE, R	1106	1044	No	4	5	1

F: female; FDG-PET: fluorodeoxyglucose-positron emission tomography; LE, L: left lower extremity; LE, R: right lower extremity; M: male; UE, L: left upper extremity; UE, R: right upper extremity.

Figure 1 (A–B) General pattern of brain metabolic alterations on FDG-PET imaging in ALS. Distribution of brain metabolic alterations in 66 ALS patients with a low motor symptom burden (A) and 65 ALS patients with a high motor symptom burden (B), compared to a cohort of 39 healthy controls. Blue indicates areas of relative hypometabolism, and orange indicates areas of relative hypermetabolism (difference only appreciable in color version). FDG-PET: fluorodeoxyglucose-positron emission tomography; L: left; R: right.

Table 3 Brain anatomical areas with significant metabolic alterations on FDG-PET imaging in 131 patients with ALS compared to healthy controls, shown separately for those with a low versus high motor symptom burden.

Right

	Cerebral/cerebellar hemisphere and Brodmann area (BA)
	BA	Left	BA
Low motor symptom burden, n = 66
Hypometabolism	Superior frontal gyrus	8/11
	Inferior frontal gyrus	9/47	Inferior frontal gyrus	47
	Medial frontal gyrus	10	Medial frontal gyrus	10
	Insula	13
			Rectal gyrus	11
	Anterior cingulate gyrus	32
Hypermetabolism	Middle occipital gyrus	18/37	Middle occipital Gyrus	19
	Cuneus	18	Cuneus	19
	Cerebellar tonsil	–	Cerebellar tonsil	–
	Cerebellar nodule	–
High motor symptom burden, n = 65
Hypometabolism	Superior frontal gyrus	8/10	Superior frontal gyrus	6
	Middle frontal gyrus	46	Middle frontal gyrus	9
	Inferior frontal gyrus	47	Inferior frontal gyrus	46
	Medial frontal gyrus	10	Medial frontal gyrus	9/10
			Insula	13
	Anterior cingulate gyrus	24/32	Anterior cingulate gyrus	24
	Lentiform nuclei	–
Hypermetabolism	Middle occipital gyrus	18/19/37	Middle occipital gyrus	19
	Inferior occipital gyrus	18
	Cuneus	18	Cuneus	18
	Uvula	–
			Pyramis	–
	Cerebellar tonsil	–

BA: Brodmann area; FDG-PET: fluorodeoxyglucose-positron emission tomography.

Figure 2 (A–B) Brain metabolic alterations on FDG-PET imaging in relation to focal weakness in ALS. Including focal weakness with and without upper motor neuron (UMN) signs (A) and only including focal weakness with concomitant UMN signs (B). Blue indicates areas of relative hypometabolism, and orange indicates relative hypermetabolism (difference only appreciable in color version). Regions that were not associated with specific alterations are shown to the left in both A and B and the regions that were associated with specific alterations (bulbar and right lower extremity, respectively) are shown to the right. The bulbar region was not included in B since UMN signs in this area are difficult to appreciate on clinical examination. FDG-PET: fluorodeoxyglucose-positron emission tomography; L: left; R: right.

Table 4 Brain anatomical areas with significant metabolic alterations on FDG-PET imaging in relation to focal motor weakness in 131 patients with ALS.

	Cerebral/cerebellar hemisphere and Brodmann area (BA)
	Right	BA	Left	BA
Bulbar weakness
Hypometabolism	Precentral gyrus	6/44	Precentral gyrus	6
			Superior frontal gyrus	6
	Middle frontal gyrus	6/9	Medial frontal gyrus	6
	Inferior frontal gyrus	45/47	Inferior frontal gyrus	45
	Superior temporal gyrus	38
			Cingulate gyrus	32
Right lower extremity weakness
Hypermetabolism	Superior temporal gyrus	38

Notes: There were significant findings for bulbar weakness irrespective of clinical signs of upper motor neuron (UMN) dysfunction, and for right lower extremity weakness when only considering weakness with concomitant clinical signs of UMN dysfunction. BA: Brodmann area; FDG-PET: fluorodeoxyglucose-positron emission tomography.

Figure 3 (A–D) Examples of brain metabolic alterations on longitudinal FDG-PET imaging in four patients with ALS. Compared to a cohort of 39 healthy controls. The findings are shown in relation to the severity of motor weakness, indicated by a color scheme, in several areas: right upper extremity, left upper extremity, right lower extremity, left lower extremity, and the bulbar region (represented by a speech bubble). In the FDG-PET imaging illustrations, blue indicates areas of relative hypometabolism whereas orange indicates relative hypermetabolism (difference only appreciable in color version). FDG-PET: fluorodeoxyglucose-positron emission tomography; L: left; R: right.

Data availability statement

Data on patient characteristics and imaging can be obtained from the original data sources or from the authors with the appropriate approval from a research ethics board.