Low Serum Thiamine Research Articles

Wernicke Encephalopathy Caused by Avoidance-Restrictive Food Intake Disorder in a Child: A Case-Based Review.

Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out.

Generalized vestibular hyporeflexia and chronic upbeat nystagmus due to thiamine deficiency.

Ocular motor and vestibular manifestations of Wernicke's thiamine deficiency (WTD) are frequent and heterogeneous. Previous neuropathological and neuroimaging findings identified brainstem and cerebellar lesions responsible for these findings, however, peripheral vestibular lesions are probably uncommon in human WTD, though noted on an avian thiamine deficient study. Single case study of a WTD patient post-gastric bypass who developed ataxia, oscillopsia and nystagmus, with low serum thiamine, and increased MRI T2 signal in the thalami, but normal brainstem and cerebellum. Vestibular evaluation showed significant vestibular hyporreflexia affecting all six canals, and a chronic upbeat nystagmus, now for 14months after WTD onset. Serial clinical, video head impulse, nystagmus analysis, cervical and ocular vestibular evoked responses. She is undergoing treatment with Memantine, Clonazepam and vestibular rehabilitation, and feels improvement. This report shows a novel combination of central and peripheral vestibular findings, of relevance for diagnosis and treatment, in addition to the development of a coherent hypothesis on the ocular motor and vestibular findings in WTD.

Thiamine Deficiency in the Pathophysiology and Diagnosis of Wernicke-Korsakoff Syndrome: Case Report and Literature Review

Thiamine deficiency is associated with life-threatening pathologies, as Wernicke syndrome (WS), Korsakoff syndrome (KS), Marchiafava-Bignami (MB) disease, and wet or dry beri-beri (BB). Among the etiological factors, the thiamine deficiency may be suspected in subjects at risk for malnutrition (decreased nutrient intake, increased nutrient losses, or impaired nutrient absorption). Computed tomography (CT) but especially magnetic resonance imaging (MRI) is the best method to detect diencephalic and mesencephalic cytotoxic edematous lesions in patients with acute WS, with hyperintense on long-TR spin-echo MRI imaging and low-density signal abnormalities on CT scans. We report a case of WS in an 82-year-old woman with the history of cancer and eating disorder, who presented a neurological worsening during recovery, associated with low serum thiamine levels and the presence of symmetrical areas of hyperintense signal in the long-TR sequences of MRI. After parenteral thiamine supplementation, we observed a rapid improvement of ocular and language disorders occurred, with a low and incomplete improvement of peripheral neuropathy, supporting the WS diagnosis. Our case report presented the clinical picture of WS and KS and the diagnosis was confirmed by both the laboratory tests and the brain imaging techniques. The dosage of the vitamin was useful and accurate when performed before the beginning of the supplementation therapy. This case is important in bringing to light a clinical picture often observed in many medical recovery units.

An Unusual Case of Thiamine Deficiency in a Total Parenteral Nutrition-Dependent Child Secondary to Munchausen by Proxy

An Unusual Case of Thiamine Deficiency in a Total Parenteral Nutrition-Dependent Child Secondary to Munchausen by Proxy

SUN-596 A Rare Presentation of Early Onset Wernicke Encephalopathy Following Sleeve Gastrectomy

Background: Wernicke encephalopathy (WE) has been reported after malabsorptive bariatric surgeries but is an uncommon complication of sleeve gastrectomy. Since 2011, the number of patients receiving a sleeve gastrectomy has tripled, with almost 60% of patients undergoing bariatric surgery receiving a sleeve gastrectomy in 2017 (1). We present a case of WE in a young woman as a rare and early complication of sleeve gastrectomy. Clinical Case: A 32-year old female with a past medical history significant for hypertension, pseudotumor cerebri, and morbid obesity status post sleeve gastrectomy two months prior presented to the emergency department with complaints of blurry vision and lower extremity numbness. Physical examination showed sluggish light reflex and decreased extraocular movements. Given history of pseudotumor cerebri, patient underwent a therapeutic lumbar puncture with removal of 13 ml of CSF. Opening pressure was 20 cm of water and patient experienced no relief of her symptoms. Ophthalmology consult did not offer an explanation for the blurry vision. MRI-brain with and without contrast showed findings highly suggestive of WE. It showed faint linear symmetric hyperintensities along the bilateral mesial thalamus, dorsal midbrain and periaqueductal gray matter, which were determined to be acute in nature in comparison with a MRI performed three weeks prior. Upon further investigation, thiamine level was low at 43.6 nmol/L [66.5 – 200] confirming the diagnosis of WE. Thiamine supplementation was started immediately and patient reported improvement of her vision the next day with return to baseline in 3 days. Conclusion: There have been a handful of cases of WE reported in literature as a complication of sleeve gastrectomy. Zheng, L also reported a case of WE 7 weeks after sleeve gastrectomy (2). Although sleeve gastrectomy does not directly affect the primary absorptive pathway of thiamine in the gastrointestinal tract, it is imperative to consider WE in patients presenting with suspicious neurologic symptoms after a recent sleeve gastrectomy. WE was suspected in our case due to typical MRI findings and neurological presentation after bariatric surgery, which was later confirmed by low serum thiamine level. Early detection and thiamine supplementation resulted in complete reversal of symptoms in our patient. WE is a rare but severe and preventable consequence of bariatric surgery that warrants attention given its rapid onset and detrimental course. Reference: (1) Estimate of Bariatric Surgery Numbers, 2011-2017. (2018, June 26). Retrieved from https://asmbs.org/resources/estimate-of-bariatric-surgery-numbers. (2) Zheng, L. (2016).Wernicke Encephalopathy and Sleeve Gastrectomy. American Journal of Therapeutics, 23(6).

Nonalcoholic Thiamine-Related Encephalopathy (Wernicke-Korsakoff Syndrome) Among Inpatients With Cancer: A Series of 18 Cases

Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric syndrome caused by thiamine deficiency. Cancer predisposes to thiamine deficiency through various mechanisms. Although many case reports exist on nonalcoholic WKS in cancer, larger qualitative studies are lacking. Retrospective study of patients admitted to a cancer hospital and diagnosed with WKS during routine care on a psychiatric consultation service. Only patients with at least 1 additional supporting feature (magnetic resonance imaging findings, low serum thiamine concentrations, or response to treatment) were included. Data pertaining to demographics, risk factors, phenomenology, and outcomes were abstracted from medical records by chart review. In all, 18 patients were included. All patients developed WKS during cancer treatment. Hematologic malignancy, gastrointestinal tract tumors, low oral intake, and weight loss were common risk factors. All patients presented with cognitive dysfunction, most commonly impaired alertness, attention, and short-term memory. All were diagnosed by operational criteria proposed by Caine et al., 1997 (where 2 of the following are required: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment). Few exhibited Wernicke's classic triad. Diagnostic and treatment delay were common. Only 3 patients recovered fully. Nonalcoholic WKS can occur during cancer treatment and manifests clinically as delirium. Diagnosis should be made using operational criteria, not Wernicke's triad. Most patients were not underweight and had normal serum concentration of vitamin B12 and folate. A variety of mechanisms might predispose to thiamine deficiency and WKS in cancer. Given the high frequency of residual morbidity, studies should focus on decreasing diagnostic and treatment delay.

Recurrent psychiatric manifestations in thiamine‐responsive megaloblastic anemia syndrome due to a novel mutation c.63_71 delACCGCTC in the gene SLC19A2

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a recessive condition that mainly manifests as megaloblastic anemia, hearing loss, and diabetes.1, 2 It is caused by mutations in the gene SLC19A2, which codes for a high-affinity thiamine transporter.3 Our male proband had sensorineural deafness diagnosed at 4 years of age and insulin-dependent diabetes diagnosed at 5 years. At 19 he was found to have myopia, astigmatism and decreased peripheral visual fields, as well as megaloblastic anemia with low serum thiamine level. He was started on 100 mg thiamine daily, which was later decreased to 50 mg. The proband's brother had similar features. He died at 18 years, reportedly from a heart problem. The proband had a history of inappropriate sexual behavior since the age of 13 and a long history of explosive/aggressive/assaulting behavior and transient paranoid ideations. Aggressive behavior was triggered by frustration around food items and by misperceptions and beliefs that others were ‘bad-mouthing’ him. He communicated through sign language and a few spontaneous verbalizations and was oriented x3. Irritable mood, impulsivity, and paranoid ideations were noted. Insight was impaired and judgment was fair for his mental age. A gradual decline from low–normal to mild intellectual disability was noted. Thiamine treatment during 18 months substantially decreased the frequency and severity of his explosive/aggressive episodes but did not affect his transient paranoid ideations. Multiple psychotropic medications were previously ineffective at controlling these episodes. Testing for mutations in SLC19A2 revealed homozygosity for the c.63_71delACCGCTC mutation, resulting in a frameshift and truncated protein. This mutation was not previously reported.2 To our knowledge, one other patient with TRMA and a psychotic episode was previously reported.4 This female patient had only one documented psychotic episode with mood changes. Neuropsychological manifestations related to thiamine deficiency have been well established in alcoholic populations known for nutrient deficits.5 Thiamine administration controlled the progressive encephalopathy and the explosive/aggressive behavior in our patient, but his recurrent mood disorder with paranoid ideations did not resolve with thiamine supplementation. In addition to the thiamine deficiency, the novel SLC19A2 mutation reported here may have contributed to the patient's psychotic manifestations by an unknown mechanism. No conflict of interest is reported for any of the authors. This report was partially supported by The Office of People with Developmental Disabilities of New York State. The sponsor did not have any role in the conducting or the reporting of the study. Consent was obtained from the patient's legal guardian.

Wernicke’s encephalopathy because of pancreatitis in a young boy

Editor, W ernicke’s encephalopathy (WE) is a potentially life-threatening and acute neurological disorder resulting from a lack of thiamine (vitamin B1). Early diagnosis is important to prevent morbidity and mortality. Symptoms are ocular dysfunction, ataxia and changes in consciousness. WE is often associated with alcoholism or malnutrition of the elderly, but can occur in other settings such as hyperemesis gravidarum (Leitner et al. 2006), gastric bypass surgery (Longmuir et al. 2007; Bohnsack & Patel 2010) and other causes of malnutrition (Kesler et al. 2005). WE is suspected to be underdiagnosed in children (Vasconcelos et al. 1999). We wish to present a case where the ophthalmological examination led to the early detection of WE, thereby reducing the patient’s chances of severe complications. An 11-year-old boy was referred to the ophthalmological department with a 1-week history of bilateral eye pain, intermittent diplopia and bilateral temporal headache. The mother had also noted a slight ptosis of the upper left eyelid. The patient had been diagnosed with recurring pancreatitis 5 months prior to presentation at the ophthalmological department and had been experiencing abdominal pain, nausea and vomiting for a long time. He had been discharged from the hospital 2 weeks before the ophthalmological consultation after an episode of pancreatitis, but had been troubled by daily nausea and vomiting since then. The eye examination revealed a mixed horizontal ⁄ vertical end-point nystagmus. The horizontal nystagmus was observed at right gaze and left gaze and was characterized as a coarse, moderate frequency, jerk nystagmus with fast component in the direction of gaze. The vertical nystagmus was only observed at up gaze and had the same characteristics as the horizontal nystagmus, with the exception of a smaller amplitude. In addition, there was a slight ptosis of the upper left eyelid. No malalignment of the eyes was noted. Pupillary reactions were normal, and there was no anisocoria. Funduscopic examination showed symmetrical optic nerve heads with normal appearance, and there were no signs of retinal pathology. Best corrected visual acuity was 0.8 (Snellen chart) in both eyes. The ophthalmologist advised further examination with a cerebral MRI. The images showed bilateral vasogenic brain oedema in the medial thalamus in addition to a pathologically increased and symmetrical signal in both corpora mamillaria (Fig. 1). The radiologist concluded that the changes were consistent with WE. The patient was immediately admitted to the hospital and treated with intravenous thiamine and vitamin B complex tablets. Blood tests taken before commencing treatment confirmed a low serum thiamine level of 72.5 nm (normal range 100–190 nm). One day after the initiation of treatment, the vertical nystagmus had disappeared. At 2 weeks after treatment, the ptosis was no longer apparent, but the patient still had a horizontal nystagmus. Visual acuity was unchanged. A follow-up MRI about 11 weeks after the initial examination was described as normal with complete resolution of the previously observed changes. We wish to publish this case report as a reminder of a potentially lifethreatening diagnosis where the ophthalmologist can be the first to aid in early detection and prevention of the serious consequences that WE entails.

Severe anasarca due to beriberi heart disease and diabetic nephropathy

A 40-year-old man was transferred to our hospital because of severe anasarca. He was a heavy drinker for more than 20 years, and diagnosed with diabetes mellitus 8 years earlier and treated with retinal photocoagulation 8 months earlier. He reported loss of appetite after divorce 10 months prior to admission. On admission, he presented with systemic edema and dyspnea. Chest radiography showed massive pleural effusion and cardiomegaly. Serum total protein was 5.6 g/dl, albumin 2.6 g/dl, and urinary protein excretion was 5.3 g/day. Glucose tolerance test showed normal pattern. Ultrafiltration and continuous hemofiltration resulted in loss of 40 kg body weight in 5 days. Echocardiography revealed high-output heart failure and blood tests showed low serum thiamine level of 12 ng/ml (normal, >28 ng/ml). Accordingly, the diagnosis was established as beriberi heart disease complicated with nephrotic syndrome. Treatment with 50 mg/day thiamine intravenously and 80 mg/day furosemide resulted in increase in urine output, decrease in cardiac output, resolution of pulmonary effusion, and about 70 kg body weight loss. Percutaneous renal biopsy showed nodular glomerulosclerosis, mesangial matrix expansion, and thickening of glomerular basement membrane (GBM). Immunofluorescence study showed no glomerular deposition of immunoglobulin or complement. Electron microscopy showed GBM thickening and mesangial matrix deposition without electron-dense deposits or fibrils. These findings were compatible with diabetic glomerulosclerosis. In this patient, extreme malnutrition altered glucose tolerance but, on the other hand, nephrotic syndrome associated with diabetic nephropathy made the diagnosis of beriberi heart disease difficult.

Wernicke’s encephalopathy mimicking variant Creutzfeldt-Jakob disease

A 45-year-old man from tropical Australia was admitted with subacute social withdrawal, cognitive deterioration, reduced awareness and eventual mutism. Variant Creutzfeldt-Jakob disease was considered on the basis of WHO case definition criteria including typical clinical features and MRI showing symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalami. However, tonsillar biopsy was negative. Wernicke’s encephalopathy was established on the basis of low serum thiamine on admission and eventual clinical improvement on high-dose intravenous thiamine replacement, despite initial failure to respond to the standard dose of 100 mg daily intramuscularly.

Small Bowel Bacterial Overgrowth Is a Potential Mechanism for Thiamine Deficiency Identified after Roux-En-Y Gastric Bypass Surgery

Purpose: Present evidence supports a saturable, carrier-mediated exchange mechanism for thiamine transport across jejunum. It is proposed that thiamine deficiency after gastric bypass surgery results from prolonged nausea and emesis. We observed that individuals after gastric bypass surgery developed thiamine deficiency and elevation of serum folate levels, a proposed marker for small bowel bacterial overgrowth. We hypothesized that small bowel bacterial overgrowth interferes with absorption of thiamine from the small intestine. Methods: We performed a retrospective review of consecutive patients who underwent Roux-en-Y gastric bypass surgery from 2002–2004 in our institution. To eliminate immediate, post-operative changes, we included patients who received evaluation at 3 months or longer after surgery. There were 75 patients with determination of serum thiamine and folate levels. This included 48 females and 27 males with an average age of 46 years (range 21 to 68). Five patients with low serum thiamine and elevated serum folate levels had undergone glucose-hydrogen breath testing. Results: There were 37 patients with serum folate levels greater than the upper limit of normal; among these patients, 23 (62%) had serum thiamine levels below the lower limit of normal. There were 38 patients with serum folate levels within normal range; 11 (29%) had serum thiamine levels below the lower limit of normal (Chi-squared test comparing thiamine deficiency in the normal folate group to the elevated folate group: p< .01). All 5 patients who underwent glucose-hydrogen breath testing had abnormal findings supporting a diagnosis of small bowel bacterial overgrowth: 4 patients had a significant rise (>10 ppm) in breath hydrogen within 45 minutes after glucose ingestion, while 1 had an elevated fasting breath hydrogen level of 57 ppm. Conclusions: Thiamine deficiency is common after Roux-en-Y gastric bypass surgery. Small bowel bacterial overgrowth appears to be common after gastric bypass surgery, as determined by elevation of serum folate levels or the presence of abnormal glucose-hydrogen breath testing. The results support the hypothesis that small bowel bacterial overgrowth following gastric bypass surgery can interfere with thiamine absorption.

Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients

Patients with end-stage renal disease undergoing regular dialysis are prone to encephalopathy, but the cause is often unclear. Dialysis patients are at risk for thiamine deficiency, which may mimic many uremic complications, including encephalopathy. To determine whether unexplained encephalopathy in regular dialysis patients is associated with thiamine deficiency, we conducted a prospective study that enrolled 30 consecutive dialysis patients with altered mental status admitted to a referred hospital during a 1-year period. A complete history, physical and neurological examinations, laboratory investigations, and computed tomographic scans or magnetic resonance imaging of the brain were obtained for each subject. In 10 of the 30 patients, diagnoses remained obscure after the initial workup. Manifestations included confusion, chorea, acute visual loss, rapidly progressive dementia, myoclonus, convulsions, and coma. Intravenous thiamine was administered to these 10 patients. All 10 patients had thiamine deficiency confirmed by a marked response to thiamine supplementation and/or a low serum thiamine concentration (35.3 ± 6.0 nmol/L; normal, >50 nmol/L). Nine patients recovered, but one patient failed to respond because of delayed treatment. We conclude that in regular dialysis patients, unexplained encephalopathy can be mainly attributed to thiamine deficiency. This condition is fatal if unrecognized and can be successfully treated with prompt thiamine replacement. © 2001 by the National Kidney Foundation, Inc.