Neuroimaging of the Wernicke-Korsakoff syndrome

Abstract

Aim: Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition.

Methods: Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance.

Results: Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion.

Conclusions: Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.

Fig. 1

CT and MR images of an acute 35-year-old man with schizophrenia and acute nutritional deficiency-induced WE. (A) Axial CT at the level of the lateral ventricles. (B–E) Axial MR images at a similar level to the CT. (B) A proton density-weighted image. (C) A T2-weighted late-echo fast spin echo (FSE) image. (D) A fluid-attenuated inversion recovery (FLAIR) image. (E) A diffusion-weighted image (DWI). Note the hyperintensity of the fornix and thalamus, especially in D and E, less so in C, and lack of lesion conspicuity in A and B.

Fig. 2

Three contiguous FLAIR images (5 mm thick with a 2.5 mm skip) of the acute WE case in Fig. 1. Note the hyperintense signal in the mammillary bodies and colliculi (left), periventricular gray matter (middle), and fornix and thalamus (right).

Fig. 3

Surface rendered brains (top) and rendered ventricular system (bottom, green) of a 59-year-old healthy man (A and C) and a 53-year-old man with WKS (B and D). Note the shrinking of the cortical gyri and widening of the sulci (B) and expansion of the ventricles (D) of the WKS compared with the control (A and C).

Fig. 4

T1-weighted SPoiled GRadient echo (SPGR) images of the healthy (left panel) and WKS (right panel) men in Fig. 3. Note the shrunken mammillary bodies (arrows) in the WKS (B and D) compared with the control (A and C).

Fig. 5

(a) Mean ± SE of volumes of brain structures considered to subserve memory for new information: healthy controls (white), uncomplicated alcoholics (gray) and alcoholic WKS (black). All volumes are expressed as standardized Z-scores, adjusted for normal variation in intracranial volume and age. The expected value of the controls is 0 (standard deviation = 1); low values of volume in the alcoholic and WKS groups reflect volume deficits. A graded effect of uncomplicated alcoholism to WKS is present for each of these brain structures but is statistically significant for the mammillary bodies and hippocampus. These four brain structures are considered to contribute to the support of declarative memory, that is, memory for new information; profound impairment in declarative memory is characteristic of WKS. (b) Mean ± SE of volumes of brain stem structures. The pons, cerebellar hemispheres and vermis each demonstrate a trend toward a graded effect from uncomplicated alcoholism to WKS.

Fig. 6

Left: T2-weighted late-echo fast spin echo (FSE) images of a thiamine-deficient (TD) WE model in rats. Animals were treated with pyrithiamine (top images of each panel) or thiamine supplementation (bottom images of each panel). Images on the left of each panel are pre-treatment (pre-TD); images in the middle are early post-treatment (post-TD); and images on the right are late post-treatment (late post-TD) after thiamine repletion. Early post-TD, hyperintense lesions are prominent in the thiamine-deficient (pyrithiamine-treated) rats in the thalamus, mammillary nuclei and inferior colliculi. Late post-TD after thiamine repletion, the thalamus showed some recovery, the mammillary nuclei remained affected and the inferior colliculi showed complete recovery.