- Email: [email protected]
Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient
Clinical Neurology and Neurosurgery 164 (2018) 1–4
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient Salvatore Di Marco, Laura Pilati, Filippo Brighina, Brigida Fierro, Giuseppe Cosentino
MARK
⁎
Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Italy
A R T I C L E I N F O
A B S T R A C T
Keywords: Wernicke’s encephalopathy Korsakoff’s syndrome Beriberi Thiamine deficiency Vitamin B1
Thiamine (vitamin B1) deficiency is a common condition in alcohol abusers, which can lead to damage of both the peripheral and the central nervous systems. Here we describe the case of an alcoholic patient who presented with acute onset of ataxia, severe weakness of the four limbs, and hypoesthesia and dysesthesia of the distal portion of the upper and lower extremities. The clinical picture also included mental confusion and amnesia. A diagnosis of Wernicke-Korsakoff syndrome was made based on clinical symptoms and brain RMI findings. Electromyography and electroneurography revealed signs of subacute axonal sensory-motor polyneuropathy that were compatible with a rare acute presentation of beriberi. Patient immediately received parenteral thiamine administration, which resulted in rapid clinical amelioration of ataxia and confusion and also in a significant improvement of motor and sensory deficits. The association between Wernicke-Korsakoff syndrome and acute axonal polyneuropathy is a very rare condition that could make less recognizable the clinical picture of a thiamine deficiency. However, the diagnosis of thiamine deficiency should be suspected in every alcoholic patient presenting with acute onset symptoms of central and/or peripheral nervous system involvement. This because the immediate replacement treatment can be life-saving and reverse the clinical symptoms.
1. Introduction Thiamine deficiency (TD) classically presents as Wernicke’s encephalopathy (WE), which is clinically characterized by the triad of ophthalmoplegia, ataxia and confusion. This pathological condition may be associated with the Korsakoff’s syndrome (KS), an amnestic disorder characterized by anterograde and retrograde amnesia. Nutritional polyneuropathy, also called beriberi, represents another typical clinical manifestation of thiamine (vitamin B1) hypovitaminosis. Beriberi polyneuropathy (PN) is usually chronic, though rarely it can have an acute-subacute course [1]. TD is considered to be rare in the western world, where it is observed mainly in alcoholic patients. However, due to an increase of alcohol abuse in the industrialized countries, it is conceivable that neurological symptoms of hypovitaminosis B1 will be seen increasingly often. 2. Case report Here we describe the case of a 53-year-old man who was admitted to the emergency room in January 2016 for subacute onset of confusion and walking difficulties that forced him to bed. In his medical history the patient had a major depressive episode in 1998. It was around this
⁎
time when he began abusing alcohol (1–2 liters of wine/day). Family members of the patient reported that he presented with irregular sleepwake cycle, also associated with episodes of nocturnal psychomotor agitation and diurnal confusion, during the last few weeks. Irregular eating and poor nutrition with weight loss in the last few months were also reported. Gait disturbances were due to weakness of the lower limbs and balance impairment which occurred less than one month before, and then rapidly worsened in the next few weeks. The patient also complained muscle pain, cramps at the lower extremities, and burning paresthesias in hands and feet. The neurological examination showed disorientation in time and space as well as attention deficit. The cranial nerve exam was normal except for a hypophonic voice. No alterations in eye movements or nystagmus were detected. Patient was unable to sit, stand and walk due to truncal ataxia and severe muscular weakness of the lower limbs. Although to a less extent, proximal and distal weakness was also present in the upper limbs. Areflexia, hypotonia and distal muscular atrophy were recorded in all four limbs. Sensory examination showed thermodolorific and tactile hypoesthesia of the extremities, mainly in the lower limbs, and also decreased vibration sense below the level of the knees. Finally, the patient exhibited bilateral dysmetria on finger-to-nose and heel-to-knee testing that worsened
Corresponding author at: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC) University of Palermo Via del Vespro 143 90127, Palermo, Italy. E-mail address: [email protected] (G. Cosentino).
https://doi.org/10.1016/j.clineuro.2017.11.006 Received 8 September 2017; Received in revised form 17 October 2017; Accepted 7 November 2017 Available online 08 November 2017 0303-8467/ © 2017 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 164 (2018) 1–4
S. Di Marco et al.
was immediately started and continued for 7 days. Patient also received intravenous immunoglobulin (400 mg/kg for five days) remaining the possibility of a primary immune-mediated polyneuropathy. Already 24–48 h after thiamine administration confusion and truncal ataxia significantly improved, thus enabling the patient to sit without support. Although to a less extent, also the strength of the four limbs gradually improved over the next days. Two weeks later, at discharge from the hospital, the patients was able to stand and take a few steps with a single support. After the state of mental confusion was improved, a neuropsychological test battery was carried out that revealed a severe amnestic syndrome characterized by inability to form new memories, loss of past memories, and confabulation, so that a diagnosis of Wernicke-Korsakoff syndrome (WKS) was made. Oral thiamine supplementation of 300 mg/day was continued for about six months after discharge from hospital and then stopped as the patient was no longer dependent on alcohol and followed a various dietary regimen. At a follow-up examination performed eight months later, the patient was able to walk without support, presenting only mild signs of gait ataxia and steppage. Weakness significantly improved at legs and disappeared at the upper limbs. Global hypoesthesia and dysesthesia at distal extremities were recorded and a mild dysmetria was shown only at the lower limbs. Though the amnestic symptoms also improved over time, they were still present having a significant impact on patient’s social life and working ability. At a first follow-up MRI performed 10 days from admission the previously described lesions decreased (Fig. 1B), to be no longer apparent at a 6-month follow-up (Fig. 1C). A 6-month follow-up electroneurographic assessment showed a marked improvement in motor and sensory conduction parameters (Table 1), while electromyography of the same muscles as before showed no signs of denervation, but only reinnervation predominant in the distal muscles confirming regenerating processes.
Table 1 Values of neural conduction measurements recorded at first assessment and at 6-month follow-up. Nerve
First NCS
6-month follow-up NCS
Normal values
Median − left DML (ms) CMAP Amp (mV) MNCV (m/s) BE − Wrist II Dig DSL (ms) SNAP (μV) SNCV (m/s)
3.1 4.0 45.2 – – –
3.0 8.9 52.7 2.4 8.6 60.4
≤4.0 ≥5.0 ≥49 ≤3.5 ≥20 ≥47
Ulnar − left DML (ms) CMAP Amp (mV) MNCV (m/s) BE − Wrist MNCV (m/s) AE − BE V Dig DSL (ms) SNAP (μV) SNCV (m/s)
2.4 2.9 47.5 49.0 1.9 7.0
2.1 9.3 53.2 55.0 1.9 7.6 63.8
≤3.3 ≥5.0 ≥50
Tibial − left DML (ms) CMAP Amp (mV) MNCV (m/s) Knee − Ankle
5.6 0.3 41.8
3.8 3.8 40.0
≤5.6 ≥5.0 ≥40
Peroneal − left DML (ms) CMAP Amp (mV) MNCV (m/s) BK − Ankle MNCV (m/s) AK − BK
– – – –
5.1 0.6 41.4 42.0
≤5.8 ≥2.0 ≥40
Sural − left SNAP (μV) SNCV (m/s)
– –
8.5 41.0
≥8.0 ≥40
≥47 ≥17 ≥50
AE: above elbow; AK: above knee; Amp: amplitude; BE: below elbow; BK: below knee; CMAP: compound motor action potential; DML: distal motor latency; Dig: digit; DSL: distal sensory latency; Lat: latency; NCS: nerve conduction study; MNCV: motor nerve conduction velocity; SNCV: sensory nerve conduction velocity; SNAP: sensory nerve action potential.
3. Discussion The patient we describe presented with a very rare association of WKS and subacute sensory-motor axonal PN. To our knowledge very few cases have been reported so far, in which a WKS occurred in strict temporal relationship with an acute polyneuropathy, and only in one single case by Ishibashi et al. TD was due to alcohol abuse [2]. However, differently from our case, in the patient by Ishibashi et al. [2] the polyneuropathy was “reversible” as the symptoms and the electrophysiological abnormalities rapidly recovered. Our patient fulfilled the European Federation of Neurological Societies (EFNS) criteria for clinical diagnosis of WE, requiring a least two of the following: dietary deficiencies, eye signs, cerebellar dysfunction, and altered mental status or mild memory impairment. The diagnosis was further supported by the distinctive MRI findings and by the rapid clinical response to treatment with parenteral thiamine, though this was administered at a lower dose than that, up to 1500 mg daily, proposed by some authors [3]. Although thiamine levels were not assessed in our patient, it is to note that finding of low thiamine level is not a mandatory criterion for the diagnosis. A peculiarity of the present case is the subacute course of the polyneuropathy that occurred in strict temporal relationship with the other symptoms of WKS. Neuropathy due to thiamine deficiency usually develops gradually over a period of at least few months. However, patients have been described in whom the peripheral nervous system involvement mimicked a Guillain-Barrè Syndrome [1]. This may pose a problem for the treatment choice as an immune-mediated pathophysiology cannot be rule out at all. Thus, in our case an intravenous immunoglobulin treatment was also performed. However, some clues suggested that the neuropathy was likely due to a nutritional deficiency. Among these, clinical symptoms such as myalgia, cramps and burning paresthesias in the extremities that occurred in a chronic alcoholic patient together with other typical manifestations of TD, and electrophysiological findings of acute axonal neuropathy. It is
when the eyes were shut. Routine blood tests (including complete blood count, conventional renal and liver function tests, folic acid and B12 vitamin levels, ammonium and thyroid function measurements) and urine tests were all within normal limits except for a slight decrease in serum albumin levels (3.1 g/dL). The search for anti-ganglioside and anti-neuronal antibodies was negative, and the cerebrospinal fluid (CSF) analysis revealed only a slight increase in the protein levels (60 mg/dL), with normal white blood cell count (5 cells/mmc) and absence of oligoclonal bands. The patient underwent an electroencephalogram (EEG), that showed a generalized slow (theta) activity, and a electromyography/ electroneurography (EMG/ENG) examination. This latter showed a significant decrease in the amplitude of sensory nerve action potentials (SNAP) and compound motor action potentials (CMAP) or even absence of motor and sensory responses (Table 1). No signs of demyelization or motor conduction blocks were recorded. High-amplitude fibrillation potentials and positive sharp waves were recorded bilaterally in the brachioradialis, first interosseus, vastus lateralis and anterior tibialis muscles, predominantly in the distal muscles of the four limbs. Based on EMG/ENG findings a diagnosis of subacute axonal sensory-motor polyneuropathy was made. Computed Tomography (CT) scan of the brain was also performed, which was normal. Thus patient underwent a brain Magnetic Resonance Imaging (MRI) which showed areas of abnormally high signal on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images adjacent to the third ventricle bilaterally and in correspondence of the midbrain roof and the periaqueductal region (Fig. 1A). Based on clinical and instrumental findings, we made a diagnosis of WE associated with subacute axonal polyneuropathy, and a treatment with parenteral administration of 100 mg thiamine per day 2
Clinical Neurology and Neurosurgery 164 (2018) 1–4
S. Di Marco et al.
Fig. 1. Axial fluid-attenuated inversion-recovery (flair) RMI brain sections performed at the time of hospitalization (A), 10 days later (B) and at 6-month follow-up (C). A) On the left: abnormal hyperintensity in the mesial dorsal thalami. On the right: hyperintense signal in the periaqueductal gray matter. B) Abnormal hyperintensity signals both in the mesial dorsal thalami and in the periaqueductal gray matter reduced. C) The previously described lesions were no longer apparent.
factors has been taken into account [4]. Moreover, in alcoholic patients it may be difficult to determine what may be the role of direct toxic effects of ethanol or its metabolites, though evidence has been provided that alcoholic neuropathy and thiamine-deficiency neuropathy are distinct forms from both a clinical and pathological point of view [5]. In our patient, we cannot exclude a preexistent alcoholic neuropathy since patient had never performed a NCS before admission to our hospital. However, family members of the patient denied a pre-existing condition of muscle atrophy or any patient complaints about abnormal superficial
noteworthy, however, that cases of subacute beriberi neuropathy have been described in which symptoms typically associated with TD, such as WE, were not present [4]. This can make even challenging the recognition of a thiamine deficiency as a casual factor of the neuropathy and thus delay the treatment with serious risks to the life of the patient. The pathophysiological mechanisms responsible for the large interindividual differences in susceptibility to the development of TDrelated disorders, as well as those related to the variability in the clinical presentation, remain largely unclear, and the role of genetic 3
Clinical Neurology and Neurosurgery 164 (2018) 1–4
S. Di Marco et al.
interest in relation to this research and its publication.
sensation, or uncomfortable or painful burning sensations. Furthermore, we could not exclude that as in other pathological conditions affecting the PNS, the nerve damage due to TD could have favoured the development of autoimmune responses. Thus future studies should be needed to clarify to which extent the treatment with intravenous immunoglobulin could improve the prognosis of these patients when combined with the thiamine replacement treatment. In conclusion, the physician needs to remember that neuropathy due to TD can also present as an acute process. Furthermore, along with patients with history of alcohol abuse, other subjects with poor nutritional status due to different causes, e.g. chronic diseases, total parenteral nutrition, prolonged hyperemesis, bariatric bypass surgery or anorexia, should be considered at risk. In all these cases, an early diagnosis and treatment of TD is imperative to prevent and treat life threatening conditions such as WKS and severe axonal polyneuropathy.
References [1] N. Hammond, Y. Wang, M. Dimachkie, et al., Nutritional Neuropathies, Neurol. Clin. 31 (2) (2013) 477–489. [2] S. Ishibashi, T. Yokota, T. Shiojiri, et al., Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency? J. Neurol. Neurosurg. Psychiatry 74 (5) (2003) 674–676. [3] A.D. Thomson, C.C. Cook, R. Touquet, J.A. Henry, Royal college of physicians, London, The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department, Alcohol Alcohol. 37 (6) (2002) 513–521. [4] H. Koike, S. Ito, S. Morozumi, et al., Rapidly developing weakness mimicking Guillain-Barré syndrome in beriberi neuropathy: two case reports, Nutrition 24 (7–8) (2008) 776–780. [5] H. Koike, M. Iijima, M. Sugiura, et al., Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy, Ann. Neurol. 54 (1) (2003) 19–29.
Conflict of interest The authors declare that they have no financial or other conflicts of
4
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient Salvatore Di Marco, Laura Pilati, Filippo Brighina, Brigida Fierro, Giuseppe Cosentino
MARK
⁎
Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Italy
A R T I C L E I N F O
A B S T R A C T
Keywords: Wernicke’s encephalopathy Korsakoff’s syndrome Beriberi Thiamine deficiency Vitamin B1
Thiamine (vitamin B1) deficiency is a common condition in alcohol abusers, which can lead to damage of both the peripheral and the central nervous systems. Here we describe the case of an alcoholic patient who presented with acute onset of ataxia, severe weakness of the four limbs, and hypoesthesia and dysesthesia of the distal portion of the upper and lower extremities. The clinical picture also included mental confusion and amnesia. A diagnosis of Wernicke-Korsakoff syndrome was made based on clinical symptoms and brain RMI findings. Electromyography and electroneurography revealed signs of subacute axonal sensory-motor polyneuropathy that were compatible with a rare acute presentation of beriberi. Patient immediately received parenteral thiamine administration, which resulted in rapid clinical amelioration of ataxia and confusion and also in a significant improvement of motor and sensory deficits. The association between Wernicke-Korsakoff syndrome and acute axonal polyneuropathy is a very rare condition that could make less recognizable the clinical picture of a thiamine deficiency. However, the diagnosis of thiamine deficiency should be suspected in every alcoholic patient presenting with acute onset symptoms of central and/or peripheral nervous system involvement. This because the immediate replacement treatment can be life-saving and reverse the clinical symptoms.
1. Introduction Thiamine deficiency (TD) classically presents as Wernicke’s encephalopathy (WE), which is clinically characterized by the triad of ophthalmoplegia, ataxia and confusion. This pathological condition may be associated with the Korsakoff’s syndrome (KS), an amnestic disorder characterized by anterograde and retrograde amnesia. Nutritional polyneuropathy, also called beriberi, represents another typical clinical manifestation of thiamine (vitamin B1) hypovitaminosis. Beriberi polyneuropathy (PN) is usually chronic, though rarely it can have an acute-subacute course [1]. TD is considered to be rare in the western world, where it is observed mainly in alcoholic patients. However, due to an increase of alcohol abuse in the industrialized countries, it is conceivable that neurological symptoms of hypovitaminosis B1 will be seen increasingly often. 2. Case report Here we describe the case of a 53-year-old man who was admitted to the emergency room in January 2016 for subacute onset of confusion and walking difficulties that forced him to bed. In his medical history the patient had a major depressive episode in 1998. It was around this
⁎
time when he began abusing alcohol (1–2 liters of wine/day). Family members of the patient reported that he presented with irregular sleepwake cycle, also associated with episodes of nocturnal psychomotor agitation and diurnal confusion, during the last few weeks. Irregular eating and poor nutrition with weight loss in the last few months were also reported. Gait disturbances were due to weakness of the lower limbs and balance impairment which occurred less than one month before, and then rapidly worsened in the next few weeks. The patient also complained muscle pain, cramps at the lower extremities, and burning paresthesias in hands and feet. The neurological examination showed disorientation in time and space as well as attention deficit. The cranial nerve exam was normal except for a hypophonic voice. No alterations in eye movements or nystagmus were detected. Patient was unable to sit, stand and walk due to truncal ataxia and severe muscular weakness of the lower limbs. Although to a less extent, proximal and distal weakness was also present in the upper limbs. Areflexia, hypotonia and distal muscular atrophy were recorded in all four limbs. Sensory examination showed thermodolorific and tactile hypoesthesia of the extremities, mainly in the lower limbs, and also decreased vibration sense below the level of the knees. Finally, the patient exhibited bilateral dysmetria on finger-to-nose and heel-to-knee testing that worsened
Corresponding author at: Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC) University of Palermo Via del Vespro 143 90127, Palermo, Italy. E-mail address: [email protected] (G. Cosentino).
https://doi.org/10.1016/j.clineuro.2017.11.006 Received 8 September 2017; Received in revised form 17 October 2017; Accepted 7 November 2017 Available online 08 November 2017 0303-8467/ © 2017 Elsevier B.V. All rights reserved.
Clinical Neurology and Neurosurgery 164 (2018) 1–4
S. Di Marco et al.
was immediately started and continued for 7 days. Patient also received intravenous immunoglobulin (400 mg/kg for five days) remaining the possibility of a primary immune-mediated polyneuropathy. Already 24–48 h after thiamine administration confusion and truncal ataxia significantly improved, thus enabling the patient to sit without support. Although to a less extent, also the strength of the four limbs gradually improved over the next days. Two weeks later, at discharge from the hospital, the patients was able to stand and take a few steps with a single support. After the state of mental confusion was improved, a neuropsychological test battery was carried out that revealed a severe amnestic syndrome characterized by inability to form new memories, loss of past memories, and confabulation, so that a diagnosis of Wernicke-Korsakoff syndrome (WKS) was made. Oral thiamine supplementation of 300 mg/day was continued for about six months after discharge from hospital and then stopped as the patient was no longer dependent on alcohol and followed a various dietary regimen. At a follow-up examination performed eight months later, the patient was able to walk without support, presenting only mild signs of gait ataxia and steppage. Weakness significantly improved at legs and disappeared at the upper limbs. Global hypoesthesia and dysesthesia at distal extremities were recorded and a mild dysmetria was shown only at the lower limbs. Though the amnestic symptoms also improved over time, they were still present having a significant impact on patient’s social life and working ability. At a first follow-up MRI performed 10 days from admission the previously described lesions decreased (Fig. 1B), to be no longer apparent at a 6-month follow-up (Fig. 1C). A 6-month follow-up electroneurographic assessment showed a marked improvement in motor and sensory conduction parameters (Table 1), while electromyography of the same muscles as before showed no signs of denervation, but only reinnervation predominant in the distal muscles confirming regenerating processes.
Table 1 Values of neural conduction measurements recorded at first assessment and at 6-month follow-up. Nerve
First NCS
6-month follow-up NCS
Normal values
Median − left DML (ms) CMAP Amp (mV) MNCV (m/s) BE − Wrist II Dig DSL (ms) SNAP (μV) SNCV (m/s)
3.1 4.0 45.2 – – –
3.0 8.9 52.7 2.4 8.6 60.4
≤4.0 ≥5.0 ≥49 ≤3.5 ≥20 ≥47
Ulnar − left DML (ms) CMAP Amp (mV) MNCV (m/s) BE − Wrist MNCV (m/s) AE − BE V Dig DSL (ms) SNAP (μV) SNCV (m/s)
2.4 2.9 47.5 49.0 1.9 7.0
2.1 9.3 53.2 55.0 1.9 7.6 63.8
≤3.3 ≥5.0 ≥50
Tibial − left DML (ms) CMAP Amp (mV) MNCV (m/s) Knee − Ankle
5.6 0.3 41.8
3.8 3.8 40.0
≤5.6 ≥5.0 ≥40
Peroneal − left DML (ms) CMAP Amp (mV) MNCV (m/s) BK − Ankle MNCV (m/s) AK − BK
– – – –
5.1 0.6 41.4 42.0
≤5.8 ≥2.0 ≥40
Sural − left SNAP (μV) SNCV (m/s)
– –
8.5 41.0
≥8.0 ≥40
≥47 ≥17 ≥50
AE: above elbow; AK: above knee; Amp: amplitude; BE: below elbow; BK: below knee; CMAP: compound motor action potential; DML: distal motor latency; Dig: digit; DSL: distal sensory latency; Lat: latency; NCS: nerve conduction study; MNCV: motor nerve conduction velocity; SNCV: sensory nerve conduction velocity; SNAP: sensory nerve action potential.
3. Discussion The patient we describe presented with a very rare association of WKS and subacute sensory-motor axonal PN. To our knowledge very few cases have been reported so far, in which a WKS occurred in strict temporal relationship with an acute polyneuropathy, and only in one single case by Ishibashi et al. TD was due to alcohol abuse [2]. However, differently from our case, in the patient by Ishibashi et al. [2] the polyneuropathy was “reversible” as the symptoms and the electrophysiological abnormalities rapidly recovered. Our patient fulfilled the European Federation of Neurological Societies (EFNS) criteria for clinical diagnosis of WE, requiring a least two of the following: dietary deficiencies, eye signs, cerebellar dysfunction, and altered mental status or mild memory impairment. The diagnosis was further supported by the distinctive MRI findings and by the rapid clinical response to treatment with parenteral thiamine, though this was administered at a lower dose than that, up to 1500 mg daily, proposed by some authors [3]. Although thiamine levels were not assessed in our patient, it is to note that finding of low thiamine level is not a mandatory criterion for the diagnosis. A peculiarity of the present case is the subacute course of the polyneuropathy that occurred in strict temporal relationship with the other symptoms of WKS. Neuropathy due to thiamine deficiency usually develops gradually over a period of at least few months. However, patients have been described in whom the peripheral nervous system involvement mimicked a Guillain-Barrè Syndrome [1]. This may pose a problem for the treatment choice as an immune-mediated pathophysiology cannot be rule out at all. Thus, in our case an intravenous immunoglobulin treatment was also performed. However, some clues suggested that the neuropathy was likely due to a nutritional deficiency. Among these, clinical symptoms such as myalgia, cramps and burning paresthesias in the extremities that occurred in a chronic alcoholic patient together with other typical manifestations of TD, and electrophysiological findings of acute axonal neuropathy. It is
when the eyes were shut. Routine blood tests (including complete blood count, conventional renal and liver function tests, folic acid and B12 vitamin levels, ammonium and thyroid function measurements) and urine tests were all within normal limits except for a slight decrease in serum albumin levels (3.1 g/dL). The search for anti-ganglioside and anti-neuronal antibodies was negative, and the cerebrospinal fluid (CSF) analysis revealed only a slight increase in the protein levels (60 mg/dL), with normal white blood cell count (5 cells/mmc) and absence of oligoclonal bands. The patient underwent an electroencephalogram (EEG), that showed a generalized slow (theta) activity, and a electromyography/ electroneurography (EMG/ENG) examination. This latter showed a significant decrease in the amplitude of sensory nerve action potentials (SNAP) and compound motor action potentials (CMAP) or even absence of motor and sensory responses (Table 1). No signs of demyelization or motor conduction blocks were recorded. High-amplitude fibrillation potentials and positive sharp waves were recorded bilaterally in the brachioradialis, first interosseus, vastus lateralis and anterior tibialis muscles, predominantly in the distal muscles of the four limbs. Based on EMG/ENG findings a diagnosis of subacute axonal sensory-motor polyneuropathy was made. Computed Tomography (CT) scan of the brain was also performed, which was normal. Thus patient underwent a brain Magnetic Resonance Imaging (MRI) which showed areas of abnormally high signal on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images adjacent to the third ventricle bilaterally and in correspondence of the midbrain roof and the periaqueductal region (Fig. 1A). Based on clinical and instrumental findings, we made a diagnosis of WE associated with subacute axonal polyneuropathy, and a treatment with parenteral administration of 100 mg thiamine per day 2
Clinical Neurology and Neurosurgery 164 (2018) 1–4
S. Di Marco et al.
Fig. 1. Axial fluid-attenuated inversion-recovery (flair) RMI brain sections performed at the time of hospitalization (A), 10 days later (B) and at 6-month follow-up (C). A) On the left: abnormal hyperintensity in the mesial dorsal thalami. On the right: hyperintense signal in the periaqueductal gray matter. B) Abnormal hyperintensity signals both in the mesial dorsal thalami and in the periaqueductal gray matter reduced. C) The previously described lesions were no longer apparent.
factors has been taken into account [4]. Moreover, in alcoholic patients it may be difficult to determine what may be the role of direct toxic effects of ethanol or its metabolites, though evidence has been provided that alcoholic neuropathy and thiamine-deficiency neuropathy are distinct forms from both a clinical and pathological point of view [5]. In our patient, we cannot exclude a preexistent alcoholic neuropathy since patient had never performed a NCS before admission to our hospital. However, family members of the patient denied a pre-existing condition of muscle atrophy or any patient complaints about abnormal superficial
noteworthy, however, that cases of subacute beriberi neuropathy have been described in which symptoms typically associated with TD, such as WE, were not present [4]. This can make even challenging the recognition of a thiamine deficiency as a casual factor of the neuropathy and thus delay the treatment with serious risks to the life of the patient. The pathophysiological mechanisms responsible for the large interindividual differences in susceptibility to the development of TDrelated disorders, as well as those related to the variability in the clinical presentation, remain largely unclear, and the role of genetic 3
Clinical Neurology and Neurosurgery 164 (2018) 1–4
S. Di Marco et al.
interest in relation to this research and its publication.
sensation, or uncomfortable or painful burning sensations. Furthermore, we could not exclude that as in other pathological conditions affecting the PNS, the nerve damage due to TD could have favoured the development of autoimmune responses. Thus future studies should be needed to clarify to which extent the treatment with intravenous immunoglobulin could improve the prognosis of these patients when combined with the thiamine replacement treatment. In conclusion, the physician needs to remember that neuropathy due to TD can also present as an acute process. Furthermore, along with patients with history of alcohol abuse, other subjects with poor nutritional status due to different causes, e.g. chronic diseases, total parenteral nutrition, prolonged hyperemesis, bariatric bypass surgery or anorexia, should be considered at risk. In all these cases, an early diagnosis and treatment of TD is imperative to prevent and treat life threatening conditions such as WKS and severe axonal polyneuropathy.
References [1] N. Hammond, Y. Wang, M. Dimachkie, et al., Nutritional Neuropathies, Neurol. Clin. 31 (2) (2013) 477–489. [2] S. Ishibashi, T. Yokota, T. Shiojiri, et al., Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency? J. Neurol. Neurosurg. Psychiatry 74 (5) (2003) 674–676. [3] A.D. Thomson, C.C. Cook, R. Touquet, J.A. Henry, Royal college of physicians, London, The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department, Alcohol Alcohol. 37 (6) (2002) 513–521. [4] H. Koike, S. Ito, S. Morozumi, et al., Rapidly developing weakness mimicking Guillain-Barré syndrome in beriberi neuropathy: two case reports, Nutrition 24 (7–8) (2008) 776–780. [5] H. Koike, M. Iijima, M. Sugiura, et al., Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy, Ann. Neurol. 54 (1) (2003) 19–29.
Conflict of interest The authors declare that they have no financial or other conflicts of
4