A non-alcoholic Wernicke’s encephalopathy case with atypical MRI findings: Clinic versus radiology

Abstract

Wernicke's Encephalopathy is an acute neuropsychiatric syndrome that can be seen in both alcohol abusers and non-alcoholic population as a result of thiamine deficiency. We herein report a non-alcoholic patient with typical clinical presentations but atypical MRI findings. Early clinical suspicion of WE is especially important in non-alcoholic patients with atypical MRI findings. The diagnosis of this group is more difficult to make and the prognosis of the syndrome mostly depends on early initiation of thiamine supplementation.

Introduction

Wernicke’s encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine deficiency.¹ The classical symptom triad involves encephalopathy, oculomotor dysfunction, and gait ataxia. The syndrome can be seen in both alcoholic and non-alcoholic population. The diagnosis of non-alcoholic WE seems more difficult due to the atypical course. We herein report a non-alcoholic patient with a typical clinical presentation but atypical MRI findings.

Case report

A 36-year-old woman, diagnosed as ulcerative colitis (UC) a month previously, was referred to our clinic because of double vision, dizziness, tremor of the limbs, slurred speech, ataxia, and disorientation with delusion periods at night. Her medical history revealed birth delivery via caesarean section 7 months ago followed by fecal urgency, tenesmus, and bloody diarrhea with mucous periods. She was diagnosed as UC and treatment with peroral 5-aminosalicylic acid (5-ASA) (mesalazine) was started. However, her complaints became vigorous with additional symptoms involving severe nausea, vomiting, loss of appetite and poor food intake. She became an inpatient of gastroenterology department with further laboratory investigations of abdominal computerized tomography (CT), ultrasonography (USG), endoscopic biopsy revealing active UC. Due to her recurrent, severe, treatment resistant nausea and vomiting periods, esophagogastroduodenoscopy with biopsy was performed and revealed candida esophagitis. She was under treatment of 5-ASA both orally and rectally, intravenous (IV) methylprednisolone and IV fluconazole since then.

Her neurological examination revealed time disorientation, bilateral conjugated horizontal gaze palsy, severe truncal ataxia, and action tremor of the limbs. Delusions at nights were also noted for the first 3 days of her clinical observation. Fundoscopic examination revealed perivascular retinal hemorrhages (Figure 1). Short cognitive evaluation battery score was 47/60. Blood biochemistry analysis revealed elevated levels of liver function tests (ALP 178 U/L, GGT 238 U/L), acute phase reactants (CRP 8.89 mg/dL, ESR 45 mm/h), and low hematocrit (27.4%) levels. Serum ammoniac level was 112 mcg/dL. Sodium and potassium levels were normal (Na: 141 meq/dL, K: 3.4 meq/dL). Cranial magnetic resonance imaging (MRI) performed on the second day of her complaints revealed bilateral frontal, temporal, and parieto-occipital cortico-subcortical hyperintensities on T-2 weighted fluid attenuated inversion recovery (FLAIR) sequences. Only the left temporo-parietal lesion showed increased apparent diffusion coefficient (ADC). Diffusion weighted images (DWI) were normal and the lesions did not show contrast enhancement (Figure 2). No lesions involving medial thalami, mammillary bodies, or brain stem was present. The electroencephalogram was normal. The cerebrospinal fluid (CSF) examination revealed mild increase in protein level (48.2 mg/dL) and 20 leukocyte/mm³ on direct microscopy. Other biochemical parameters were normal. Bacteriological, mycological, and mycobacteriological incubations revealed no cellular growth. Further CSF investigation results for toxoplasmosis, toxocariasis, brucellosis, herpes simplex virus infection, and syphilis were also normal.

Figure 1.

Fundus photography, bilateral retinal hemorrhages.

Figure 2.

(a) Fluid attenuated inversion recovery (FLAIR) sequences: bilateral frontotemporal, parieto-occipital, and left temporo-parietal cortico-subcortical hyperintensities. (b) T-2 weighted images, left temporo-parietal hyperintensity. (c) Increased apparent diffusion coefficient (ADC) of the left temporo-parietal lesion. (d) No diffusion restriction on diffusion weighted images (DWI).

Depending on the typical clinical triad (encephalopathy, oculomotor dysfunction, and gait ataxia) and Caine’s criteria (dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, and altered mental status or mild memory impairment),^2,3 she was diagnosed as WE and high dose IV thiamine (1500 mg/day) was given for 16 days. Her route of dietary supplement was changed from parenteral nutrition to enteral one.

During follow up nausea, vomiting and diarrhea stopped. On the 15th day of her admission, her oculomotor abnormalities and speech recovered, truncal ataxia and action tremor decreased, making her possible to walk on her own. Her MRI findings also returned to normal (Figure 3).

Figure 3.

Normal MRI findings after thiamine supplementation.

Taking the advice of the gastroenterology department, IV methylprednisolone administration was stopped after tapering, the patient was discharged, and taken on follow-up for neurology and gastroenterology clinics under the treatment of 5-ASA.

Discussion

WE is an acute neuropsychiatric syndrome resulting from thiamine deficiency and is associated with significant morbidity and mortality.¹ Early recognition is important. The prognosis of this reversible condition critically depends on the onset time of thiamine supplementation. The syndrome has first been described by Carl Wernicke in 1881 as acute superior hemorrhagic poliencephalitis in two alcohol misusing men and a non-alcoholic young woman with pyloric stenosis, ingestion of sulfuric acid, and persistent vomiting.¹ His well-known triad is characterized by nystagmus and ophtalmoplegia, mental changes, and unsteadiness of gait. In 1997, Caine et al. reported additional criteria for chronic alcohol abusers which suggest WE diagnosis in patients with two of the proposed tetrad ‘dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, altered mental status or mild memory impairment’.^1,2 The diagnosis of non-alcoholic WE is usually more difficult than that of alcoholics. Some studies mention about only 20% or less possible premortal WE diagnosis in non-alcoholics. The autopsy series have revealed the prevalence of WE as 0.8–2.8%, which is higher than the predictions of clinical studies reporting 0.04–0.13%.¹

The typical MRI findings of WE are symmetrical involvement of medial thalami, mammillary bodies, tectal plate, and periaqueductal gray matter. Atypical MRI findings are also present, including symmetric alterations of the cerebellum, its vermis, cranial nerve nuclei (mostly CN VI, VII, VIII, and XII), red nuclei, dentate nuclei, splenium, and cerebral cortex,³ as was the case in our patient with cortico-subcortical lesions. With little exceptional case reports atypical findings are mostly seen in non-alcoholic patients.² The clinical picture in our patient was due to recurring vomiting episodes and poor food intake during the course of UC. Reversible cytotoxic edema is considered as the most distinctive lesion of WE. The heterogeneity of MRI lesions may result from disease severity, acuteness and timing of imaging. It cannot be determined which of the MRI techniques used is most useful.⁴ Rapid correction of hyponatremia can cause pontine and extrapontine lesions by osmotic changes leading to vasogenic edema. However, sodium levels in our patient were normal all through the course of the disease.⁵ The role of cortical involvement in prognosis of WE is still marked by debate. There are reports associating cortical lesions with poor prognosis due to the underlying pathophysiology of irreversible damage.⁶ On the other hand, favorable outcomes have also been reported.⁶ Similarly, our patient showed major recovery of the clinical and complete recovery of the MRI findings after two weeks of IV thiamine supplementation.

Fundoscopic signs, such as telangiectatic peripapillary nerve fiber layer with retinal hemorrhages,⁷ as observed in our patient, or nasal disc swelling and intraretinal hemorrhages in WE all regressing after thiamine supplementation,⁶ are also rarely reported. The pathophysiology is still unclear. Impaired mitochondrial functions in retinal ganglion cells and capillaries or necrosis of optic nerve cells and myelinated structures in optic nerve resulting with edema are the speculative theories reported.⁷

As there is no specific routine laboratory test available or a specific diagnostic tool including neuroimaging studies, clinical suspicion of WE is especially important in non-alcoholic patients with atypical MRI findings and the prognosis mostly depends on early initiation of thiamine supplementation.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

All authors declare that they have no conflict of interest.