Teaching Case

A 22-year-old male with autism spectrum disorder and a history of eating disorders was presented to the emergency department due to abdominal pain, reduced communication, and refusal to eat or drink for 4 days. While he was hospitalised, he developed cognitive decline and his mental status changed.

Initial investigation with CT revealed a haemorrhage in the dorsomedial aspect of the thalami, extending into the third and lateral ventricles with subsequent hydrocephalus and trans-ependymal oedema (Figure 1a). CT angiography and venography were normal, and ruled out large vessel occlusion, vascular malformation, or deep cerebral vein thrombosis.

A subsequent MRI scan revealed the same haemorrhagic findings with obstructive hydrocephalus (Figure 1b). Moreover, high signal intensity in T2 and FLAIR images with contrast enhancement at the periaqueductal area, tectal plate and posterior aspect of the brain stem (Figures 2a, 2b, 2c, 3a, 3b and 4), mammillary bodies (Figure 4), and the uncus of the temporal lobes (Figure 3a) were observed. These findings, together with the clinical and medical history, suggested the diagnosis of Wernicke’s encephalopathy with thalamic and intraventricular haemorrhage.

Background

Wernicke’s encephalopathy (WE) is an acute neurological disorder resulting from thiamine (vitamin B1) deficiency. The most common cause of the deficiency is alcoholism, but it can also be secondary to malnutrition or to factors that disrupt its absorption or mobilisation [1].

Thiamine is involved in maintaining osmotic gradients at the cellular level, in glucose metabolism, and in neurotransmitter synthesis. Deficiency causes micropathological changes and leads to defective blood brain barrier, particularly in the periventricular regions [1].

Clinical Perspective

Clinical diagnosis of WE often relies on the classical triad consisting of ocular signs, altered consciousness, and ataxia. However, studies have shown that only a minority of patients with WE present with this classic triad, which explains why it is often clinically underdiagnosed [2]. A newer classification requires at least two of the following four criteria to indicate clinical diagnosis of WE: dietary deficiencies, oculomotor abnormalities, cerebellar dysfunction, and an altered mental state or mild memory impairment [3].

Biomarkers, including an assay for thiamine, are not typically available, and no study has clearly described the sensitivity, specificity, and accuracy of thiamine levels in relation to active disease [4]. In this case, the patient received thiamine replacement therapy before blood levels were measured, and thus, thiamine levels were unknown.

The role of imaging in the disease is mainly to complement the clinical presentation and to assess the extent of disease involvement.

Imaging Perspective

Radiological features are mainly observed on MR imaging and include high signal intensity on T2-weighted images, in bilateral and symmetrical fashion, reflecting oedema. The anatomic regions most frequently involved are the dorsomedial thalami and the periventricular area of the third ventricle (where osmotic gradients are strictly related to the concentration of thiamine levels). Other common areas involved are the mamillary bodies, tectal plate, and periaqueductal area [1].

Contrast enhancement can frequently be seen in these areas in a variable manner. Diffusion restriction can occasionally be seen as well, but this may be related to the timing of the MR imaging in relation to the initial insult. Other less typical CNS locations have also been reported as being affected in a minority of cases [5].

Either gross haemorrhage at the affected locations or intraventricular haemorrhage (IVH), mainly in the third ventricle, has been reported in rare cases [6]. In those reported cases there was a relation to rapid thiamine depletion in patients with nutritional deficiency.

Outcome

In the following weeks, the patient deteriorated neurologically despite retrieval of the IVH and the thalamic haemorrhage on follow-up CT scans. An extra ventricular drain was inserted for the hydrocephalus, which was later removed. During hospitalisation he developed high-grade fever, probably of pulmonary origin, eventually leading to septic shock. Unfortunately, the patient passed away 10 weeks following his initial presentation.

Take Home Message

Bilateral symmetrical haemorrhage in the thalami with IVH involving the third ventricle, especially in patients prone to thiamine deficiency and when no vascular cause is found, should prompt further investigation into clinical or imaging signs of Wernicke’s encephalopathy (WE).

All patient data have been completely anonymised throughout the entire manuscript and related files.