Waddling Gait: A complication of valproate therapy and a thought beyond vitamin D deficiency.

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency.

Intestine-specific deletion of metal transporter Zip14 (Slc39a14) causes brain manganese overload and locomotor defects of manganism.

Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole body Zip14-knockout (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload and motor dysfunction. Initially, it was believed that Mn accumulation due to ZIP14 mutations was caused by impaired hepatobiliary Mn elimination. However, liver-specific Zip14-KO mice did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus, we hypothesized that basolaterally localized ZIP14 in enterocytes provides another route for the elimination of Mn. Using wild-type and intestine-specific Zip14-KO (I-KO) mice, we have shown that ablation of intestinal Zip14 is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14-mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions and brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinal Zip14 expresssion likely could contribute to the Parkinson-like Mn accumulation of manganism.NEW & NOTEWORTHY Mn-induced parkinsonism is recognized as rising in frequency because of both environmental factors and genetic vulnerability; yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 in Mn excretion.

A botanical drug composed of three herbal materials attenuates the sensorimotor gating deficit and cognitive impairment induced by MK-801 in mice.

OBJECTIVES: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801. METHODS: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task. KEY FINDINGS: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3ß expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg). CONCLUSIONS: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3ß signalling pathways.

[Peripheral neuropathy with hypervitaminosis B6 caused by self-medication]. / Neuropathie périphérique avec hypervitaminose B6 provoquée par l'automédication.

INTRODUCTION: Vitamin B6 is contained in a number of over-the-counter drugs and vitamin supplements. It may cause severe neurological troubles in case of overdosage. CASE REPORT: We report the case of a 92-year-old women with gait disorders. A diagnosis of peripheral neuropathy with both motor and sensitive deficits was established and investigated. Blood level of vitamin B6 was measured to investigate a potential deficiency. Unexpectedly, the results showed hypervitaminosis B6, which appears to be due to self-administration of an over-the-counter drug containing vitamin B6. Discontinuation of this drug was associated with decrease in vitamin B6 level as well as gait improvement. We also discuss the toxicity of vitamin B6. CONCLUSION: Hypervitaminosis B6 remains a possible cause of peripheral neuropathy and it may be caused by self-administration of over-the-counter vitamin-containing drugs.

Peripheral Neuropathy Due to Recreational Use of Nitrous Oxide Presenting After an Ankle Sprain With Foot Drop.

A 22-year-old man was referred for orthopedic follow-up after an ankle injury. Initial evaluation in urgent care included radiographs with negative findings. After a delayed presentation, a course of functional treatment was recommended. Subsequently, he developed a deep venous thrombosis and pulmonary emboli. He was found to be factor V Leiden deficient and was fully anticoagulated on warfarin. Later reevaluation revealed a steppage gait and foot drop. Electrodiagnostic studies (ie, electromyography and nerve conduction studies) revealed a severe peripheral polyneuropathy. The patient admitted to engaging in high-volume recreational use of nitrous oxide. Neurological evaluation confirmed vitamin B12 deficiency consistent with the toxic effects of nitrous oxide. The patient's condition improved with vitamin B supplementation, bracing, and avoidance of nitrous oxide and similar neurotoxins. He participated in a 3-month physical rehabilitation program, and he displayed partial recovery at most recent follow-up. [Orthopedics. 2018; 41(3):e432-e433.].

Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Nitrous Oxide-induced Subacute Combined Degeneration Presenting with Dystonia and Pseudoathetosis: A Case Report.

PURPOSE: Nitrous oxide (N2O) is neurotoxic by interfering with vitamin B12 bioavailability. The clinical picture is indistinguishable to that of subacute combined degeneration (SCD). A movement disorder might occur though it is not a characteristic feature. We report a patient with N2O-induced SCD, exhibiting a combination of different involuntary movements. CASE REPORT: A 20-year-old woman presented with one month of progressive unsteady gait, involuntary movements and tingling sensation in a stocking-glove distribution. She had used N2O and ketamine intermittently for recreational purposes for about two years. Neurological examination demonstrated normal cranial nerve functions except for dystonia in the facial muscle and tongue. Her muscle strength was full, but there were bilateral hyperreflexia and extensor plantar response. She exhibited dystonia in four limbs with athetoid movement in fingers and toes, worsened by eye closure. Vibration and proprioception were impaired. Laboratory tests revealed anemia (Hb: 9.9 g/dl) with normal mean corpuscular volume (85.7 fL) and decreased iron level (22 µg/dl) while other results were normal including serum vitamin B12 level (626 pg/ml). Magnetic resonance imaging showed a hyperintense lesion from C1 to C6 level in the posterior column. She was diagnosed as having SCD caused by N2O abuse, presenting with generalized dystonia and pseudoathetosis. The involuntary movements disappeared with vitamin B12 supplementation. CONCLUSION: Movement disorders may be the rare manifestations of SCD associated with N2O abuse. Early recognition of the etiology is vital because it is treatable with vitamin B12 and methionine.

Postnatal alterations in GABAB receptor tone produce sensorimotor gating deficits and protein level differences in adulthood.

The GABA transmitter system plays a vital role in modulating synaptic formation and activity during development. The GABAB receptor subtype in particular has been implicated in cell migration, promotion of neuronal differentiation, neurite outgrowth, and synapse formation but it's role in development is not well characterized. In order to investigate the effects of brief alterations in GABAB signaling in development, we administered to rats the GABAB agonist baclofen (2.0mg/kg) or antagonist phaclofen (0.3mg/kg) on postnatal days 7, 9, and 12, and evaluated sensorimotor gating in adulthood. We also examined tissue for changes in multiple proteins associated with GABAB receptor function and proteins associated with synapse formation. Our data indicate that early postnatal alterations to GABAB receptor-mediated signaling produced sex differences in sensorimotor gating in adulthood. Additionally, we found differences in GABAB receptor subunits and kalirin protein levels in the brain versus saline treated controls. Our data demonstrate that a subtle alteration in GABAB receptor function in early postnatal life induces changes that persist into adulthood.

Repeated but not acute treatment with ∆9-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D2/3 receptor antagonist haloperidol.

Cannabis produces cognitive dysfunctions that resemble those of schizophrenia; yet the neurobiological substrate of this similarity remains unclear. Schizophrenia patients show deficits in prepulse inhibition (PPI) of the acoustic startle reflex (ASR), an operational measure of the information-processing abnormalities that may underlie the cognitive and positive symptoms of the disease. However, the effect of cannabis on PPI remains poorly understood, as data are often contradictory. Here, we investigated the effect of acute and repeated treatment with ∆(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on PPI in rats, and the role of dopamine D2/3-receptor blockade in this effect. PPI and ASR were sequentially measured after the first and the last dose of a 21-days treatment with THC (1 mg/kg/day) or vehicle and at 1-week following discontinuation of treatment. The effect of haloperidol (0.1 mg/kg) on THC-induced PPI alteration was also evaluated. Chronic, but not acute, THC treatment produced significant reductions in PPI that were normalized back to control values within one-week of THC discontinuation. The THC-induced gating deficits were observed in the absence of ASR change and were reversed by the D2/3-receptor antagonist haloperidol. Chronic THC exposure induced PPI disruptions that emerged only following repeated administrations, suggesting that time-dependent neuroadaptations within the DA mesolimbic system are involved in the disruptive effects of THC on sensorimotor gating. These gating deficits were transient and appeared to be dependent on an overactivity of D2/3-receptor-mediated dopamine signaling, highlighting a potential role for D2/3-receptors in the propsychotic action of THC.

Panax ginseng is neuroprotective in a novel progressive model of Parkinson's disease.

Panax ginseng has been used in traditional Chinese medicine for centuries. Among its various benefits is a pluripotent targeting of the various events involved in neuronal cell death. This includes anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Indeed, ginseng extract and its individual ginsenosides have been demonstrated to influence a number of biochemical markers implicated in Parkinson's disease (PD) pathogenesis. We have reported previously that administration of the ginseng extract, G115, afforded robust neuroprotection in two rodent models of PD. However, these traditional rodent models are acute in nature and do accurately recapitulate the progressive nature of the disease. Chronic exposure to the dietary phytosterol glucoside, ß-sitosterol ß-d-glucoside (BSSG) triggers the progressive development of neurological deficits, with behavioral and cellular features that closely approximate those observed in PD patients. Clinical signs and histopathology continue to develop for several months following cessation of exposure to the neurotoxic insult. Here, we utilized this model to further characterize the neuroprotective effects of the ginseng extract, G115. Oral administration of this extract significantly reduced dopaminergic cell loss, microgliosis, and accumulation of α-synuclein aggregates. Further, G115 administration fully prevented the development of locomotor deficits, in the form of reduced locomotor activity and coordination. These results suggest that ginseng extract may be a potential neuroprotective therapy for the treatment of PD.

Effects of manganese from a commercial multi-trace element supplement in a population sample of Canadian patients on long-term parenteral nutrition.

BACKGROUND: Long-term parenteral nutrition (PN) can be associated with micronutrient deficiency or toxicity depending on supplementation. Recently, hypermanganesemia and potential neurological toxicity were reported. The aim of this study was to assess the effect of manganese supplementation in a sample of patients on long-term PN receiving manganese (Mn) as part of a multi-trace element (TE) supplement. METHODS: A convenience sample of 16 patients underwent clinical and blood biochemical measurements as well as magnetic resonance imaging (MRI) of the brain. Descriptive statistics were performed. RESULTS: The mean daily Mn supplementation was 7.28 ± 0.97 µmol/d (400 ± 53 µg/d), which was within the American Medical Association Nutrition Advisory Group guidelines of 2.73-14.56 µmol/d (150-800 µg/d) but exceeded the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) 2002 recommendations of 1.09-1.82 µmol/d (60-100 µg/d). The mean whole blood Mn level was 1.38 ± 0.29 times the upper limit of normal (ULN), and 8 of 14 patients with blood measurements had Mn levels above ULN. On MRI, 81% of patients had high signals on T1-weighted images assumed to be Mn deposits in their basal ganglia. Two patients with positive MRI (15%) had a clinical diagnosis of Parkinson disease. Multiple neuropsychiatric complaints were reported, including depression (66%), lack of concentration (42%), memory disturbances (17%), and gait instability (8%). CONCLUSION: These results suggest that Mn status is elevated in these patients. Manganese supplementation should be used with caution in patients receiving long-term PN, and attention should be paid to the Mn content of multi-TE supplements.

Chronic tryptophan deprivation attenuates gating deficits induced by 5-HT(1A), but not 5-HT2 receptor activation.

The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts a multifaceted function in the modulation of information processing, through the activation of multiple receptor families. In particular, stimulation of 5-HT(1A) and 5-HT(2A) receptors leads to sensorimotor gating impairments and perceptual perturbations. Previous evidence has shown that chronic deprivation of L-tryptophan (TRP), the precursor of 5-HT, results in marked reductions of 5-HT brain levels, as well as neuroplastic alterations in 5-HT(1A) and 5-HT(2A) expression and/or signaling. Building on these premises, in the present study we tested whether a prolonged TRP deprivation may differentially impact the roles of these receptors in the regulation of the prepulse inhibition (PPI) of the acoustic startle reflex, a dependable index of gating. Male Sprague-Dawley rats were fed for 14 days with either a regimen with negligible TRP content (TR-) or the same diet supplemented of TRP (TR+). At the end of this schedule, rats were treated with the prototypical 5-HT(1A) receptor agonist 8-OH-DPAT (62.5-250 µg/kg, subcutaneous, s.c.) or the 5-HT2 receptor agonist DOI (0.25-1 mg/kg, s.c.). Notably, the PPI deficits induced by 8-OH-DPAT in TR- rats were significantly milder than those observed in their TR+ counterparts; these effects were fully prevented by the 5-HT(1A) antagonist WAY-100135 (10 mg/kg, intraperitoneal). Conversely, TRP deprivation did not affect the PPI-disrupting properties of DOI. These findings suggest that prolonged 5-HT depletion attenuates the influence of 5-HT(1A), but not 5-HT2 receptors on sensorimotor gating, confirming the distinct mechanisms of these two targets in PPI regulation.

Examination of ketamine-induced deficits in sensorimotor gating and spatial learning.

Subanesthetic administration of the NMDA receptor antagonist ketamine has been suggested to have utility in several therapeutic domains; however, its recreational use has exceeded its therapeutic applications. Ketamine has been utilized to investigate NMDA receptor-mediated learning and memory and to model disorders such as schizophrenia. The utility of ketamine in relation to schizophrenia is based on a proposed mechanism of the disorder being associated with reduced NMDA receptor function within a subset of GABAergic neurons. The examination of ketamine with relevance to the above topics has produced valuable data; however, there exists a great deal of variability in the literature regarding dosage and timing of administration to examine ketamine-induced deficits. In the below experiments we sought to identify the minimal subanesthetic dosage and schedule of ketamine administrations that would produce behavioral deficits in multiple tasks with relevance to the above investigations. We evaluated sensorimotor gating as well as spatial learning and memory in the Morris water task utilizing different doses of ketamine. Our data indicate that an 8 mg/kg subcutaneous dose of ketamine was the minimal dose to produce impairments in both sensorimotor gating and spatial learning.

Myelopathy secondary to copper deficiency as a complication of treatment of Wilson's disease.

Wilson's Disease (WD) is an autosomal recessive disorder of copper metabolism resulting in a pathological accumulation of this metal, initially in the liver and later in other organs, mainly brain. Treatment with copper chelating agents and zinc salts results in a depletion of copper deposits and prevents or reverses the clinical manifestations. Copper deficiency may cause haematological and neurological changes, the latter principally being polyneuropathy and myelopathy. We report a patient with WD who developed a myelopathy associated with a deficiency of copper following prolonged treatment with D-penicillamine and zinc salts.

T-817MA, a novel neurotrophic agent, ameliorates loss of GABAergic parvalbumin-positive neurons and sensorimotor gating deficits in rats transiently exposed to MK-801 in the neonatal period.

T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] is a newly synthesized neuroprotective agent for the treatment of psychiatric disorders characterized by cognitive disturbances, such as Alzheimer's disease. Cognitive impairment has also been suggested to be a cardinal feature of schizophrenia. We sought to determine whether T-817MA would ameliorate sensorimotor gating deficits and loss of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) neurons in the brain of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor blocker, in the neonatal stage, as an animal model of schizophrenia. Prepulse inhibition (PPI) was examined in rats treated neonatally with MK-801 (postnatal day; PD 7-10, 0.2 mg/kg/day, s.c.) or vehicle at PD 35 and PD 63. The number of PV-positive GABAergic neurons in the medial prefrontal cortex (mPFC) and the hippocampus was measured after the behavioral assessments. T-817MA (10 or 20 mg/kg) or vehicle was administered for 14 days (on PD 49-62). Administration of T-817MA at 20 mg/kg, but not 10 mg/kg, ameliorated PPI deficits and completely reversed the decrease in the number of PV-positive GABAergic neurons in rats given MK-801. These results indicate that T-817MA may provide a novel therapeutic approach for the treatment of cognitive deficits of schizophrenia.

Lesions of the rat entopeduncular nucleus further deteriorate N-methyl-D-aspartate receptor antagonist-induced deficient prepulse inhibition.

Lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), have been shown to improve deficient prepulse inhibition (PPI) induced by the dopamine agonist apomorphine. We here tested the effect of EPN lesions on the PPI-disruptive effect of the non-competitive NMDA receptor antagonist dizocilpine in rats. Neurotoxic bilateral lesions of the EPN were induced by ibotenic acid (4 µg in 0.4 µl). Rats were tested for PPI and locomotor activity after systemic injection of dizocilpine (vehicle and 0.15 mg/kg). Bilateral EPN lesions further deteriorated the PPI deficit induced by dizocilpine, while locomotion was not affected. This work indicates that the EPN is an important brain region within the neuronal circuit responsible for NMDA receptor antagonist-induced PPI deficits.

The role of endogenous neurotensin in psychostimulant-induced disruption of prepulse inhibition and locomotion.

The neuropeptide neurotensin (NT) is closely associated with dopaminergic and glutamatergic systems in the rat brain. Central injection of NT into the nucleus accumbens (NAcc) or peripheral administration of NT receptor agonists, reduces many of the behavioral effects of psychostimulants. However, the role of endogenous NT in the behavioral effects of psychostimulants (e.g. DA agonists and NMDA receptor antagonists) remains unclear. Using a NTR antagonist, SR142948A, the current studies were designed to examine the role of endogenous NT in DA receptor agonist- and NMDA receptor antagonist-induced disruption of prepulse inhibition of the acoustic startle response (PPI), locomotor hyperactivity and brain-region specific c-fos mRNA expression. Adult male rats received a single i.p. injection of SR142948A or vehicle followed by D-amphetamine, apomorphine or dizocilpine challenge. SR142948A had no effect on baseline PPI, but dose-dependently attenuated d-amphetamine- and dizocilpine-induced PPI disruption and enhanced apomorphine-induced PPI disruption. SR142948A did not significantly affect either baseline locomotor activity or stimulant-induced hyperlocomotion. Systemic SR142948A administration prevented c-fos mRNA induction in mesolimbic terminal fields (prefrontal cortex, lateral septum, NAcc, ventral subiculum) induced by all three psychostimulants implicating the VTA as the site for NT modulation of stimulant-induced PPI disruption. Further characterization of the NT system may be valuable to find clinical useful compounds for schizophrenia and drug addiction.

Manganese toxicity in a child with iron deficiency and polycythemia.

A previously healthy 5-year-old girl presented with pica, emotional lability, and marked gait abnormalities. She had concurrent severe iron deficiency and polycythemia. Her magnetic resonance imaging (MRI) scan showed increased signal in the basal ganglia on T1-weighted images consistent with manganese neurotoxicity. Manganism was subsequently confirmed as her blood manganese levels were extremely elevated. Chelation therapy resulted in improvement in her mobility but she continues to have significant gait impairment. An epidemiological investigation identified well water as the potential source of manganese exposure for our patient, but to date, we have been unable to identify the nature of her neurotoxic susceptibility.

Lesions of the entopeduncular nucleus in rats prevent apomorphine-induced deficient sensorimotor gating.

Dopamine-induced hyperactivity and deficient sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR), are used as animal models for neuropsychiatric disorders such as schizophrenia and Tourette's syndrome. We here investigated whether excitotoxic lesions of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve apomorphine-induced PPI-deficits and hyperactivity. Additionally, we investigated the effect of EPN lesions on cognition, motivation and motor skills. In male Sprague Dawley rats bilateral EPN lesions were induced by stereotactic injection of ibotenate (4 µg in 0.4 µl phosphate buffered saline, PBS) or sham-lesions by injection of vehicle PBS. After one week, rats were tested for learning and memory (continuous and delayed alternation, T-maze), for motivation (progressive ratio test with breakpoint of 3 min inactivity, Skinner box), and for motor skills (rotating rod). Thereafter, rats were tested for PPI of ASR (startle response system) after subcutaneous injection of apomorphine (1.0mg/kg and vehicle) and for locomotor activity (0.5mg/kg and vehicle). Ibotenate-induced EPN lesions did not affect learning and memory, motivation or motor skills. Basal locomotor activity and PPI was also not affected, but EPN lesions ameliorated apomorphine-induced hyperlocomotion and deficient PPI. This work indicates an important role of the EPN for the modulation of dopamine agonist-induced deficient sensorimotor gating and hyperlocomotion, without affecting normal behavioral function.

[An unrecognized cause of myelopathy associated with copper deficiency: the use of denture cream]. / Une cause méconnue de myélopathie par carence en cuivre: l'utilisation de pâte adhésive dentaire.

We report two patients with myelopathy associated with copper deficiency and pancytopenia. Excessive intake of zinc can lead to a severe deficiency of copper reducing the absorption of ingested copper. The patients had in common consumption of denture adhesive paste containing zinc. In both patients, laboratory tests showed a combination of copper deficiency, hyperzincemia and increased urinary zinc level. The use of a denture cream was stopped. Copper supplementation, initially subcutaneously then oral corrected the copper deficiency and pancytopenia. Clinically, the pain faded but the gait disturbance persisted. Copper deficiency associated with the use of denture cream rich in zinc is an unrecognized cause of myelopathy associated with pancytopenia which should be diagnosed early to establish appropriate therapeutic measures to minimize neurological complications.