β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet

Article Figures & Data

Download figure
Open in new tab
Download powerpoint
Fig 1.
Voxel-of-interest (inner 8 × 8 matrix) and masked region (7 × 7 matrix) that retained spectra based on SNR, NAA, and adequate Cramér-Rao bounds. Across the brain (spectra labeled A–F, corresponding to labeled voxels in image at the upper right), 2 peaks comprising lactate and BHB are shown at 1.33 and 1.2 ppm, respectively, with lactate more prominent in voxels containing CSF in this patient with mitochondrial cytopathy. At the lower right, the composite spectrum from the masked region is shown, with the LCModel fit overlaid.
Download figure
Open in new tab
Download powerpoint
Fig 2.
Scatterplot of blood serum BHB concentrations (milligrams/deciliter) versus brain BHB/NAA and BHB/Cr ratios demonstrates the strong associations between measures.

Table 1:

Patient clinical data including underlying epilepsy syndrome, seizure type, and antiepileptic medications

Patient	Age (yr)	Epilepsy Syndrome^21–23	Seizure Type	Medications
1	1	EE (Unclassified)	T	LEV
2	2	Metabolic (Mito)	TS	ZNS/LTG/LEV
2	7	Metabolic (Mito)	TS/GTC	ZNS/LTG/LEV/RFM
2	8	Metabolic (Mito)	TS/MY/GTC	ZNS/LTG/LEV/RFM
3	9	MAE	MY/AT/GTC	VPA/CLB/RFM
4	7	Metabolic (Mito)	MY/RFL	TPM
4	10	Metabolic (Mito)	MY/RFL	TPM/ZNS
5	7	EE (MCD)	T/AT/TS	VGB/LTG
6	2	Structural (MCD)	Focal	ZNS/TPM
7	1	Structural (Aicardi)	ES	VGB
8	6	Genetic (SCN1A)	MY/AT	LEV/ETX/CLN
9	6	Metabolic (Mito)	MY/AT	LEV/LTG/ETX/CLN
10	6	MAE	T/MY/TS	LTG
11	0.5	Genetic (ATP1A3)	Focal/SE	LEV
11	1	Genetic (ATP1A3)	SUB/MY	LTG/CLB
12	6	EE (unclassified)	AT/T/GTC	CLB
13	1	EE (unclassified)	ES	VGB
14	2	Metabolic (Mito)	ES	TPM
15	4	EE (LGS)	AT/T/AA	LTG/LEV/ZNS
16	1	EE (Unclassified)	ES	ZNS/LEV
17	5	Genetic (DEAF 1)	T/AT/GTC	LEV
18	1	Metabolic (Mito)	ES	ZNS

Note:—“Epilepsy Syndrome”: EE indicates epileptic encephalopathy; Mito, primary mitochondrial disease; MAE, myoclonic astatic epilepsy; MCD, malformation of cortical development; LGS, Lennox-Gastaut Syndrome; “Seizure Type”: T, tonic; TS, tonic spasms; GTC, generalized tonic-clonic; MY, myoclonic; AT, atonic; RFL, reflexive seizure; ES, epileptic spasms; SE, status epilepticus; AA, atypical absence; SUB, subclinical seizures; “Medications”: LEV, levetiracetam; ZNS, zonisamide; LTG, lamotrigine; RFM, rufinamide; CLB, clobazam; TPM, topiramate; VGB, vigabatrin; ETX, ethosuximide; CLN, clonazepam; VPA, valproic acid.

Table 2:

Partial correlations of blood BHB concentration (mg/dL) and brain metabolite ratios derived from ¹H-MRS, using patient age in months as a covariate

Group	BHB/Cr	BHB/Cho	BHB/NAA	BHB/Lac	Cho/Cr	NAA/Cr	NAA/Cho	Lac/NAA	Lac/Cr
Lag ≤14 d (n = 13)
R	.871	.898	.886	.507	−.287	−.645	−.540	.376	.253
Significance	.000	.000	.000	.092	.367	.024	.070	.228	.428
Lag ≤30 d (n = 23)
R	.803	.814	.807	.538	−.165	−.553	−.443	.421	.334
Significance	.000	.000	.000	.010	.463	.008	.039	.051	.128
Lag ≤120 d (n = 31)
R	.790	.802	.781	.484	−.312	−.658	−.515	.523	.423
Significance	.000	.000	.000	.008	.099	.000	.004	.004	.022
All (N = 49)
R	.579	.588	.584	.393	−.170	−.387	−.312	.290	.162
Significance	.000	.000	.000	.006	.254	.007	.033	.048	.278