Deep Cerebral Venous Thrombosis Presenting with Korsakoff Syndrome

Abstract

Deep cerebral venous thrombosis (DCVT) is an uncommon cerebrovascular disease with diverse neurological deficits and a poor prognosis. Therefore, the early diagnosis and treatment of DCVT are needed. We herein present a case of DCVT with edematous lesions in the bilateral thalami with Korsakoff syndrome (KS) as the initial symptom. Although KS mainly occurs in patients with thiamine deficiency, it can also result from cerebrovascular disease. Because thalamic dysfunction may be associated with KS, DCVT with thalamic lesions should be considered a cause of KS to facilitate its early diagnosis and treatment.

Introduction

Cerebral venous sinus thrombosis (CVT) is a rare cerebrovascular disease that accounts for approximately 0.5-1.0% of all stroke cases (1). Clinical symptoms of CVT depend on the location of the cerebral venous occlusion. Deep cerebral venous thrombosis (DCVT), including thrombotic occlusion of the internal cerebral vein, vein of Galen, and straight sinus, occurs in 11% of CVT cases and demonstrates diverse neurological deficits due to lesions in the thalamus or basal ganglia (2). Because DCVT is often misdiagnosed as another medical condition (3), it is important to include this disease in the differential diagnosis to facilitate early treatment.

Korsakoff syndrome (KS) is characterized by anterograde and retrograde amnesia, disorientation, and confabulations, and is mainly caused by thiamine deficiency or malnutrition (4,5). However, some cases of KS due to other pathologies, including ischemic stroke and cerebral venous thrombosis, have been reported (6-11), and we should recognize that cerebrovascular diseases can also induce KS.

We herein report a case of DCVT presenting with bilateral thalamic lesions and subacute KS.

Case Report

A 62-year-old man was admitted to a neighboring hospital with rapidly progressive amnesia that had started one month earlier. He was an occasional drinker, had a history of paroxysmal atrial fibrillation and type 2 diabetes mellitus, and had been treated with edoxaban and metformin. He had not received finasteride or minoxidil. Brain magnetic resonance imaging (MRI) revealed abnormal intensities in the bilateral thalami, and the patient was transferred to our hospital on day 4 of hospitalization. He was alert and did not complain of headaches. Neurological investigations revealed severe anterograde and retrograde amnesia and disorientation. He also recounted fabricated events, including “My brother stabbed me in the stomach several months ago” and “I graduated from a university in Hawaii”, reflecting confabulatory behavior. His verbal comprehension was preserved, and his speech was fluent. Ophthalmoplegia, nystagmus, weakness, pyramidal signs, cerebellar ataxia, and sensory disturbances were not observed. The neuropsychological assessments are summarized in Table 1. The Mini-Mental State Examination and Hasegawa's Dementia Scale-Revised and Frontal Assessment Battery scores were 16/30, 12/30 and 9/18, respectively. The Wechsler Memory Scale-Revised revealed visual, verbal, and recent memory impairments. In the Standard Language Test of Aphasia, almost all categories, except for word fluency and Kanji word writing, were within the normal range, which did not indicate aphasia (Table 2). A blood examination revealed decreased Cbl (201 pg/mL) and mild hyperhomocysteinemia (16.7 nmol/mL). D-dimer, antithrombin III, protein S, protein C, thiamine, and folate levels were within the normal ranges. Anti-aquaporin-4, anti-myelin oligodendrocyte glycoprotein, anti-Ma2, anti-nuclear, anti-neutrophil cytoplasmic, anti-SS-A/Ro, anti-SS-B/La, anti-parietal cell, anti-intrinsic factor, and anti-Japanese encephalitis virus antibodies (hemagglutination inhibition) were negative. A cerebrospinal fluid study showed increased protein levels (121.5 mg/dL) without pleocytosis, and the levels of interleukin-6, interleukin-10 and IgG index were within normal limits. Oligoclonal bands were not observed. Electroencephalography demonstrated no abnormalities. Brain computed tomography (CT) revealed low-density lesions in the left thalamus and high-density areas in the vein of Galen (Fig. 1A). Contrast-enhanced brain MRI revealed a left lateral thalamic infarction (Fig. 1B), vasogenic edema in the bilateral thalami (Fig. 1C, D), and enhancement of bilateral thalamic lesions (Fig. 1E). A low-signal intensity area on T2*-weighted gradient-echo imaging (Fig. 2A) and contrast defects were observed in the vein of Galen (Fig. 2B, C). Magnetic resonance venography (MRV) revealed distal occlusion of the vein of Galen (Fig. 2D). Magnetic resonance angiography revealed no obstruction of the basilar artery (Fig. 2E). Cerebral digital subtraction angiography (DSA) was not performed because the patient was unable to rest. The patient was diagnosed with KS and DCVT. Since the MRI findings were not indicative of Wernicke's encephalopathy, we did not administer thiamine. Although intravenous heparin administration is recommended for acute-phase treatment of DCVT, it could not be continued due to worsening delirium. Because warfarin has a longer half-life than edoxaban and its effect could be monitored by the prothrombin time-international normalized ratio (PT-INR), he was started on oral anticoagulant therapy with warfarin instead of edoxaban with a target PT-INR of 2.6-3.0. Furthermore, considering hyperhomocysteinemia as a risk factor for DCVT, metformin was discontinued along with cobalamin replenishment to resolve cobalamin deficiency and hyperhomocysteinemia. Although the enhancement of bilateral thalamic lesions was reduced, lesions in the bilateral anterior thalamic nuclei and mediodorsal thalami and occlusion of the vein of Galen persisted (Fig. 3), while his memory impairment partially improved (Table 1). The patient was transferred for rehabilitation on day 50 of hospitalization.

Table 1.

Summary of Neuropsychological Assessments.

Measures		On admission	Post-treatment
MMSE score, points		16/30	24/30
Orientation		1/10	6/10
Registration		3/3	3/3
Attention and Calculation		5/5	5/5
Recall		0/3	1/3
Language		7/9	9/9
HDS-R score, points		12/30	17/30
Age		0/1	1/1
Orientation		1/6	5/6
Repeating three words		3/3	3/3
Serial subtractions		2/2	2/2
Digits backward		1/2	0/2
Recalling three words		1/6	3/6
Recalling five objects		3/5	2/5
Generating vegetables		1/5	1/5
FAB score, points		9/18	17/18
Conceptualization		1/3	3/3
Mental flexibility		1/3	2/3
Programming		1/3	3/3
Sensitivity to interference		1/3	3/3
Inhibitory control		2/3	3/3
Environmental autonomy		3/3	3/3
WMS-R score, points (normal range: 85-115)	Visual memory	68	101
	Verbal memory	53	70
	Attention	112	106
	Delay memory	<50	<50

MMSE: Mini-Mental State Examination, HDS-R: Hasegawa’s Dementia Scale-Revised, FAB: Frontal Assessment Battery, WMS-R: Wechsler Memory Scale-Revised

Table 2.

Details of Standard Language Test of Aphasia.

Categories		Accuracy rates, % (normal range: 80-100%)
Auditory comprehension	Auditory word recognition	100
	Sentence comprehension	100
	Follow verbal commands	100
	Kana letter discrimination	100
Speaking	Speaking object naming	95
	Word repetition	100
	Describe behaviors	100
	Explain picture story	100
	Sentence repetition	100
	Word fluency	53
	Read aloud kanji words	100
	Read aloud kana letters	100
	Read aloud kana words	100
	Read aloud short sentences	100
Reading comprehension	Kanji word-picture matching	100
	Kana word-picture matching	100
	Sentence-picture matching	100
	Follow written commands	90
Writing	Write kanji words	60
	Write kana words	80
	Narrative writing	100
	Dictate kana letters	90
	Dictate kanji words	100
	Dictate kana words	100
	Dictate short sentences	100
Calculation		85

Figure 1.

Brain computed tomography (CT) and magnetic resonance imaging (MRI) on admission. Brain CT revealed low-density lesions in the left thalamus (A, arrow) and high-density areas in the vein of Galen (A, arrowhead). Brain MRI demonstrating infarction in the left lateral thalamus on diffusion-weighted imaging (B, arrow), vasogenic edema in the bilateral thalami (C, arrowheads), hyperintense areas in the bilateral thalami on fluid-attenuated inversion recovery imaging (D, arrows), and enhancement of the bilateral thalamic lesions on contrast-enhanced T1-weighted imaging (E, arrowheads).

Figure 2.

Brain magnetic resonance imaging on admission. In the vein of Galen, a low-signal-intensity area was observed on T2*-weighted gradient-echo imaging (A, arrow) and contrast defects were observed on contrast-enhanced T1-weighted imaging (B, C, arrowheads). Magnetic resonance venography revealed loss of the internal cerebral and basal veins (D, arrow). Magnetic resonance angiography revealed no basilar artery occlusion (E).

Figure 3.

Brain magnetic resonance imaging after treatment. After anticoagulant therapy, hyperintense areas in the bilateral thalami on fluid-attenuated inversion recovery imaging (A, arrows) and enhancement of bilateral thalamic lesions were reduced on contrast-enhanced T1-weighted imaging (B, arrowheads). Occlusion of the vein of Galen remained on magnetic resonance venography (C, arrow).

Discussion

We herein describe a case of DCVT that presented with subacute KS. Thrombotic occlusion of the vein of Galen caused bilateral thalamic lesions, which may have resulted in KS. In this patient, the only risk factor for DCVT was mild hyperhomocysteinemia due to cobalamin deficiency, and the cause of DCVT was not identified. However, we considered that hyperhomocysteinemia might be a contributing factor to the development of DCVT despite direct oral anticoagulant therapy.

DCVT is a rare subtype of CVT accounting for 11% of all cases (12). As the deep cerebral venous system drains the thalamus, basal ganglia, brainstem, and deep white matter of the frontal, parietal, and temporal lobes, venous congestion induced by DCVT can lead to diverse neurological deficits including seizures, focal motor deficits, altered sensorium, visual disturbances, and gaze abnormalities (2). Therefore, these findings make the accurate diagnosis of DCVT challenging. Furthermore, DCVT is a risk factor for 30-day mortality and a poor long-term prognosis (13). An early diagnosis of DCVT is important to improve the prognosis of patients with CVT.

Imaging investigations, especially MRI, are the most sensitive modality for the diagnosis of DCVT. In DCVT, edematous lesions in the bilateral thalami are the most typical findings, accompanied by venous infarction and hemorrhage in some cases. T1-weighted imaging and T2*-weighted gradient-echo imaging are helpful in detecting venous thrombi (14,15). Furthermore, MRV and DSA are required for a definitive diagnosis and are useful if MRI findings are inconclusive (16). In the present case, edematous lesions in the bilateral thalami, a thrombus in the vein of Galen detected by T2*-weighted gradient-echo imaging and contrast-enhanced T1-weighted imaging, and venous occlusion exhibited on MRV led to the diagnosis of DCVT. Thus, DCVT should be considered in patients with bilateral thalamic lesions on MRI, and acute or subacute neurological deficits.

KS caused by DCVT has not been reported. Why does KS occur in DCVT, as in our case? While KS is mainly caused by thiamine deficiency, excessive alcohol ingestion, and malnutrition, cerebrovascular diseases, such as infarction of the thalamus and mammillothalamic tract and cavernous sinus thrombosis, can also induce KS (6-11). However, the neuropathology of KS is controversial. Although KS lesions have been reported in the anterior thalamic nucleus (11,17-22), mammillary bodies (23,24), and mediodorsal thalamic nucleus (25), it has not been determined whether the manifestation of KS requires dysfunction of the anterior thalamic nucleus alone or a combination of the mammillary bodies and mediodorsal thalamic nucleus (24). It has also been reported that disruption of the Papez circuit (hippocampal formation, mammillary bodies, anterior thalamic nucleus, cingulate cortex, fornix, mammillothalamic tract, and cingulum) and Yakovlev circuit (frontal lobe, medial temporal cortices, amygdala, and mediodorsal thalamus) may cause KS (26,27). In our case, extensive edematous lesions in the bilateral thalami due to DCVT involved both the anterior thalamic nucleus and mediodorsal thalamus, which was consistent with the culprit lesions for KS. DCVT often causes consciousness disturbance (2), and detailed neuropsychological assessments are difficult in these cases, which may explain why KS caused by DCVT has not yet been reported. However, the patient was alert, probably because of the relatively slow progression of DCVT, and a diagnosis of KS could be made.

In conclusion, we described a case of DCVT presenting with KS. Cerebrovascular diseases are also important origins of KS, and DCVT uncommonly causes KS because of thalamic and mammillothalamic tract lesions. MRI findings should be carefully evaluated to facilitate an early diagnosis and treatment of DCVT in patients with subacute KS.

The authors state that they have no Conflict of Interest (COI).

Taiga Suzuki and Yosuke Takeuchi contributed equally to this work.