The Anatomical Basis for Dystonia: The Motor Network Model

H. A. Jinnah; Vladimir Neychev; Ellen J. Hess

doi:10.5334/tohm.383

Figures & Tables

Table 1

Rodent Models with Dystonic Motor Phenotype

Genetic models	Gene	Gene Product	Phenotype	Biological Basis for Dystonia
Tottering mouse	Cacna1a	α1a subunit of P/Q-type calcium channel	Paroxysmal generalized dystonia with mild ataxia	Abnormal cerebellar Purkinje neuron activity
Leaner mouse	Cacna1a	α1a subunit of P/Q-type calcium channel	Severe generalized dystonia and ataxia	Abnormal cerebellar Purkinje neuron activity and degeneration
dt rat	Atcay	Caytaxin	Severe generalized dystonia	Abnormal cerebellar Purkinje neuron activity
DRD mouse	TH	Tyrosine hydroxylase	Diurnal dystonia	Reduced striatal dopamine
Gunn rat	Ugt1A1	Uridine diphosphate glucuronyltransferase	Bilirubin encephalopathy (kernicterus) with dystonia	Abnormal striatal neuron activity
Ip3r1 mouse	Ip3r1	Inositol trisphosphate receptor	Severe generalized dystonia	Abnormal cerebellar Purkinje neuron activity

Pharmacological models	Pharmacological agent (s)	Mode of Induction	Phenotype	CNS Alterations
Blepharospasm rat	6-OHDA	Lesion of nigral neurons combined with partial injury of the facial nerve	Sustained partial eyelid closure with increased blink rate	Abnormal basal ganglia function
Rapid-onset dystonia parkinsonism mouse	Oubain	Inhibition of cerebellar sodium/potassium pump by local microinjection	Generalized dystonia	Abnormal cerebellar Purkinje neuron activity
Cerebellar glutamate receptor activation (mouse or rat)	Kainic acid or AMPA agonists	Activation of cerebellar glutamate receptors by local microinjection	Generalized dystonia	Abnormal cerebellar Purkinje neuron activity
Levodopa-induced dyskinesia (mouse or rat)	6-OHDA Levodopa	Levodopa-induced dyskinesias following nigral neuron lesion	Trunk and limb dystonia	Abnormal striatal neuron activity
3-nitroproionic acid lesions (mouse or rat)	3-Nitroproionic acid	Lesions of striatum by local or systemic injections	Trunk and limb dystonia	Abnormal striatal neuron activity
sigma receptor ligand rat	1,3-di-o-Tolylguanidine	Microinjection into the red nucleus	Generalized dystonia	Abnormal rubral neuron activity

[i] This table selectively includes rodent models where the anatomical origin of dystonia has been well studied. It does not include many models where the anatomical source for dystonia has not been clearly established, or genetic models with no apparent dystonic motor phenotype.

[ii] Abbreviations: 6-OHDA, 6-Hydroxydopamine; AMPA, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid.

Table 2

Focal Lesion Studies in Dystonia

Type of Dystonia	Study	Source of Cases		Focal lesions
Type of Dystonia	Study	Literature Review	Chart Review	Basal Ganglia	Cortex	Thalamus	Brainstem	Cerebellum	Other
Hemidystonia	Marsden et al.79	13	28	45	1	7	0	0	Internal capsule=13
Hemidystonia	Pettigrew et al.80	0	22	11	0	1	0	0	Internal capsule=1
Mixed	Obeso and Gimenez-Roldan85	32	39	68	8	16	1	6	0
Cervical	LeDoux and Brady81	21	4	6	0	0	0	11	Spinal cord=6
Mixed	Strader et al.84	0	16	4	12	1	0	0	0
Blepharospasm	Khooshnoodi et al.82	30	18	9	1	12	11	9	Midbrain=7
Upper limb	Liuzzi et al.83	72	4	17	4	39	4	1	Spinal cord=7

[i] This table lists the locations of brain lesions in series of cases with presumed secondary dystonia. Because some cases had lesions that overlapped more than one region, the numbers of lesions may differ from the total number of cases. In cases where lesions overlapped regions, the reports sometimes listed the regions separately and sometimes combined. Several studies included a literature review, so some cases may be reported more than once.

Table 3

Voxel-based Morphometry Studies of Dystonia

Type of Dystonia	Study	Cases/Controls	Regions Affected
Type of Dystonia	Study	Cases/Controls	BG	CRB	CTX	Other
BSP	Etgen et al.148	16/16	Put (↑)		IPL (↓)
BSP	Obermann et al.149	11/14	Caud (↑)	Hem (↑)		Thal (↓)
BSP	Obermann et al.149	11/14	Put (↓)	Hem (↑)		Thal (↓)
BSP	Martino et al.150	25/24			PreF (↑)
					SMC (↓)
					STL (↓)
BSP	Suzuki et al.151	32/48			SMC (↑)
BSP	Suzuki et al.151	32/48			Cing (↑)
CCD	Piccinin et al.152	35/35		Verm (↑)
CCD	Piccinin et al.152	35/35		Hem (↓)
CCD	Piccinin et al.153	27/54		Verm (↓)	IPD (↓)	HPC (↓)
				Hem (↓)	OCC (↓)
					PMC (↓)
					SMA (↓)
					SMC (↓)
CD	Draganski et al.154	10/10	GP (↑)	Floc (↑)	PM (↑)
					SMA (↓)
					DLPFC (↓)
					OCC (↓)
CD	Egger et al.155	11/31
CD	Obermann et al.149	9/14	Caud (↑)	Hem (↑)	STL (↑)	Thal (↑)
CD	Obermann et al.149	9/14	Put (↓)	Hem (↑)	STL (↑)	Thal (↑)
CD	Draganski et al.156	29/28	Put (↑)
CD	Draganski et al.156	29/28	GP (↑)
CD	Pantano et al.157	19/28	Caud (↓)		PM (↓)
CD	Pantano et al.157	19/28	Put (↓)		SMC (↓)
CD	Prell et al.158	24/24	GP/Put (↑)		PM (↓)
					SMA (↓)
					SMC (↓)
					PreF (↑)
					OCC (↑)
CD	Bono et al.159	19/25			PM (↓)
CD	Bono et al.159	19/25			PMC (↓)
CD	Waugh et al.160	17/17
CD	Filip et al.161	25/25		Verm (↑)	PMC (↑)
CD	Filip et al.161	25/25		Hem (↑)	PMC (↑)
DYT1	Draganski et al.156	11/11	Put (↓)
FHD	Garraux et al.162	36/36			SMC (↑)
FHD	Egger et al.155	11/31	GP (↑)
FHD	Delmaire et al.163	30/30		Hem (↓)	SMC (↓)	Thal (↓)
FHD	Granert et al.89	14/14			PM (↑)
FHD	Granert et al.164	11/12	Put (↑)
FHD	Zeuner et al.165	22/28	GP (↑)
FHD	Zeuner et al.165	22/28	Put (↑)
GEN	Egger et al.155	9/31	GP (↑)
LD	Simonyan et al.166	40/40	Put (↑)	Hem (↑)	SMC (↑)
LD	Simonyan et al.166	40/40	Put (↑)	Hem (↑)	PreF (↑)
LD	Waugh et al.160	7/7

[i] Arrows show increased (↑) or decreased (↓) volumes. Studies involving multiple types of dystonia are separated according to type of dystonia rather than as a mixed group.

[ii] Abbreviations: Caud, Caudate; CCD, Craniocervical Dystonia (a mixed population of cranial dystonia, cervical dystonia and both combined); Cing, Cingulate Gyrus; DLPFC, Dorsolateral Prefrontal Cortex; Floc, Cerebellar Flocculus; GEN, Generalized Dystonia; GP, Globus Pallidus; Hem, Cerebellar Hemisphere; HPC, Hippocampus; IPL, Inferior Parietal Lobule; Pref, Prefrontal Cortex; NA, Nucleus Accumbens; OFC, Orbitofrontal Cortex; OCC, Occipital Cortex; PM, Primary Motor Cortex; Put, Putamen; SMC, Sensorimotor Cortex; STL, Superior Temporal Lobe; SMA, Supplementary Motor Area.