Dry and Wet at the Same Time. Acute Polyneuritic Beriberi Complicated by Heart Failure (Shoshin Beriberi)

Sir, Classic beriberi presents with dyspnoea, fatigue, leg edema, lower extremity weakness, and numbness. Beriberi has traditionally been divided into four separate entities; the infantile, dry, wet, and gastrointestinal beriberi.[1,2] The cardiovascular form (wet beriberi) is characterized by a high-output cardiac failure. The other extreme is an acute and fulminant variant known as “Shoshin” beriberi. It is characterized by catastrophic cardiovascular collapse and low-output cardiac failure with ventricular dilatation, anion gap metabolic acidosis, hypotension, peripheral cyanosis, and eventually death. “Shoshin” is derived from the Japanese words, “sho means acute damage and shin means heart.” Neurological (dry) beriberi is characterized by a chronic symmetrical sensori-motor axonal “dying back” (ascending or centripetal) neuropathy. Here, we report an unusual combination of an acute polyneuritic variant of dry beriberi mimicking Guillain-Barre syndrome (GBS) which was complicated by the “Shoshin” variant of wet beriberi. A 35-year-old man presented to us with numbness of both legs of 3 years duration. Recently, he had started developing spontaneous pain in the legs although otherwise the polyneuropathy remained static. For the last 2 weeks, his weakness had started progressing with increasing pain, ascending numbness and weakness of upper and lower limbs. He was unemployed, lived with his mother and had a history of chronic alcohol abuse (750 ml/day of rum), smoking, and poor food intake. On examination, he had allodynia till his knees and grade-4 power in all 4 limbs with global areflexia. His initial nerve conduction studies were suggestive of an axonal sensori-motor neuropathy affecting both lower limbs and somatosensory evoked potentials studies showed prolonged P37 and N45 latencies from both lower limbs. On day 2 after admission, he developed an acute left vocal cord palsy, bifacial weakness, neck flexor weakness, worsening weakness (3/5), dyspnea at rest, paradoxical respiration, and oliguria. His BP was 90/60 mmHg and pulse rate was 120 bpm. Initially, GBS was suspected. He was shifted to the ICU and intubated. Repeated ABGs showed severe anion gap metabolic acidosis with high serum lactate (19 mmol/L). An intra-aortic balloon pump (IABP) was inserted for severe hypotension and inotropic support with noradrenaline/vasopressin was started on day 3. Due to anuria and rising creatinine levels (9.5 mg%), he was started on sustained low-efficiency dialysis (SLED). Lung ultrasound showed “B” lines in all lung fields suggestive of diffuse interstitial lung edema. Echo showed dilatation of both atria and the right ventricle with left ventricular global hypokinesia. There was a moderate left ventricular systolic dysfunction, a moderate pericardial effusion (1.8 cm), and moderate tricuspid regurgitation (TR). The pulmonary artery systolic pressure (PASP) was elevated (50 mmmHg). Serum brain natriuretic peptide levels were 2700 pg/ml consistent with heart failure. No clots or vegetations were seen. D-dimer levels, CT pulmonary angiogram, and lower limb venous Doppler (to rule out deep vein thrombosis) were normal. On day 5, CSF analysis was normal and he was started on 900 mg of thiamine/day with multivitamin supplements. By day 6, his blood pressures stabilized to 110/70 mm Hg and echo showed improvement in biventricular function although his muscle power had worsened to grade 0/5 power with areflexia and he had new gaze-evoked nystagmus. By day 7, inotropes were discontinued and the IABP was removed although SLED was continued. A blood sepsis PCR panel, dengue, leptospira, Scrub typhus antibodies, with urine and broncho-alveolar lavage cultures were negative and thyroid function tests were normal. Septic shock was excluded based on the overall clinical picture, absence of fever and leukocytosis, and negative blood cultures. Thiamine was continued at 900 mg/day. Toxicology workup was negative. However, due to financial constraints, he was shifted to a local hospital, where he expired in 2 days while undergoing conventional dialysis due to purported “septic shock.” The incidence of thiamine deficiency has reduced dramatically as global nutrition has improved. It is now restricted to small cohorts of alcoholics, severely malnourished, patients on total parenteral nutrition, post gastrectomy patients, anorexia nervosa, hyperemesis gravidarum, or dialysis patients. The phosphorylated form of thiamine, thiamine pyrophosphate (TPP), is essential for aerobic metabolism and is a precursor for the co-factor of 2 essential enzymes in the Krebs cycle, namely, pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. A deficiency of TPP leads to the accumulation of pyruvate and lactate. This leads to anion gap metabolic acidosis with lactic acidosis and multiorgan dysfunction. Therefore, thiamine deficiency should be suspected in any patient with a sepsis-like syndrome, unexplained heart failure, anion-gap acidosis with lactic acidosis, encephalopathy, or neuropathy occurring in the setting of alcohol abuse or nutritional deprivation. We performed a literature search in Pubmed for articles in English about “Shoshin beriberi” in adults and “beriberi low-output cardiac failure.” A total of 26 articles were identified. All of them were case reports and only a single cohort had at least 10 patients, substantiating the rarity of this condition. The neurologic form is referred to as “dry beriberi” and consists of a mild chronic symmetrical axonal sensorimotor peripheral neuropathy or Wernicke–Korsakoff encephalopathy. Patients develop mild weakness, paraesthesia, and neuropathic pain. Nerve conduction studies show reduced lower limb sensory and motor responses with mild slowing of conduction velocities: an axonal sensory-motor neuropathies. Rare patients develop a rapidly progressive acute beriberi polyneuritis mimicking GBS or a critical illness polyneuropathy.[3-7] In 2 reports, thiamine responsive heart failure was found to coexist with the acute polyneuritis [Table 1].[6,7] Unlike other axonal polyneuropathies, recovery may be relatively rapid although most cases demonstrate only partial recovery. If Wernicke’s encephalopathy (WE) coexists, an acute confusional state, ataxia, or ophthalmoplegia/nystagmus can be detected and MRI will demonstrate the corresponding imaging abnormalities.[5] CSF is often normal and lacks the albumin-cytological dissociation seen with GBS.Table 1: Collated literature on adult patients with Shoshin beriberiIn “Wet beriberi,” the classic heart failure is a high-output heart failure with peripheral vasodilatation, decreased systemic vascular resistance, increased venous return and stroke volume with a hyperdynamic circulation. Progressive disease leads to myocardial damage, intractable vasodilatation followed by circulatory shock with metabolic acidosis. The other extreme, “Shoshin beriberi” is a low-output cardiac failure from the onset. Circulatory shock is seen at the onset with secondary ischemic organ injury (oliguria/anuria or ischemic hepatitis).[8] Thus, hypotension, tachycardia, and lactic acidosis are observed. Acute severe pulmonary hypertension due to increased pulmonary arterial blood flow, dilated RA/RV, and elevated LV end-diastolic pressures are found and the echo findings may mimic an acute pulmonary embolism. Pleural, pericardial effusion, pedal edema, and ascites may be seen.[9] It usually has a fulminant course and can be rapidly fatal due to multiorgan dysfunction unless recognized and treated early with thiamine. Intensive therapy with mechanical ventilation, inotropics, and vasopressors, intra-aortic balloon counterpulsation (IABP), continuous renal replacement therapy, or extracorporeal membrane oxygenation may be required to salvage patients.[4] Cardiac failure may be reversible with thiamine replacement within 1-2 days; however, recovery from the axonal polyneuropathy takes days to weeks.[10] We suggest a modification of the Blankenhorn criteria originally used for beriberi heart disease in 1946 in the current context to diagnose Beriberi[1] an enlarged heart with normal sinus rhythm, edema, and elevated venous pressure,[2] shock without any other obvious cause or with anion gap metabolic acidosis,[3] nonspecific ST-T changes in ECG,[4] echocardiography showing a reduction in LV systolic function, and LV or RV dilatation with or without valvular regurgitation or RA/RV dilatation with elevated PASP,[5]P eripheral neuropathy,[8] history compatible with dietary deficiency or loss of thiamine (e.g., through hemodialysis)[11] measurement of blood thiamine levels, pyruvate, alpha-ketoglutarate, lactate, glyoxylate levels, urinary excretion of thiamine and its metabolites or the RBC transketolase activity[12] a response to thiamine supplementation or autopsy evidence,[13] MRI findings of Wernicke’s encephalopathy[14] and no other evident cause.[11,15] Often biochemical confirmation is lacking as these tests are not widely available and have a long turn-around time. In conclusion, we described an unusual combination of a GBS variant of “dry beriberi” that was exacerbated by the “Shoshin variant” of wet beriberi. We further outline new criteria to help in the early diagnosis of beriberi. Although we were unable to biochemically confirm beriberi, the constellation of clinical features, investigations, and cardiovascular response to thiamin supplementation were sufficient for diagnosis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.