lithium-chloride and Nervous-System-Diseases

Lithium continues to be the treatment of choice for bipolar disorder. Acute lithium poisoning is a potentially serious event. We present a retrospective observational significative study of episodes of acute lithium poisoning during a 52- month period. Poisoning was defined by a blood lithium concentration of 1.5 mEq/L or higher. We analyzed treatment and epidemiologic and clinical characteristics of 70 episodes were identified (incidence density among treated patients, 1.76 per 100 patient-years). The most frequent cause of lithium poisoning was a concurrent medical condition (46%). Most poisonings were mild (74.2%), but neurologic involvement was identified in 40.3%. Electrocardiographic abnormalities were found in 8 cases. Acute renal failure, found in 23 patients (37.1%), was mild in most cases, although 11 patients required hemodialysis. We concluded that acute lithium poisoning is an uncommon complication, but risk needs to be lowered. Patients should be warned to avoid dosage errors and to take special care during concurrent illnesses and while taking other medications.. El litio sigue siendo el tratamiento de elección en el trastorno bipolar. La intoxicación aguda por litio (IAL) es un cuadro potencialmente grave. Se presenta un estudio observacional, retrospectivo de las IAL observadas durante un periodo de 52 meses. Se definió como IAL cuando se registró una concentración de litio en sangre 1,5 mEq/L. Se analizaron sus características clínicas, epidemiológicas y su tratamiento de 70 episodios de IAL (densidad de incidencia: 1,76 IAL por cada 100 pacientes tratados-año). La causa más frecuente de IAL fue un proceso patológico intercurrente (46%). La mayoría fueron de carácter leve (74,2 %), con sintomatología neurológica en el 40,3%. En 8 IAL hubo alteraciones electrocardiográficas, 23 IAL (37,1%) se asociaron con fracaso renal agudo, la mayoría de carácter leve y 11 precisaron hemodiálisis. Se concluye que la IAL es una complicación infrecuente, pero es necesario disminuir su riesgo advirtiendo al paciente ante la existencia de procesos intercurrentes, errores en la posología o polimedicación.

Topics: Acute Disease; Acute Kidney Injury; Aged; Antidepressive Agents; Bipolar Disorder; Comorbidity; Female; Humans; Lithium Chloride; Male; Middle Aged; Nervous System Diseases; Poisoning; Renal Dialysis; Retrospective Studies

Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro.

Topics: Acrylamides; Blotting, Western; Cell Differentiation; Cell Line, Tumor; Cell Survival; Densitometry; Gene Expression; Humans; Hydroxyurea; Image Processing, Computer-Assisted; Immunohistochemistry; Lithium Chloride; Microscopy, Confocal; Models, Neurological; Nervous System Diseases; Neurons; Reverse Transcriptase Polymerase Chain Reaction; Teratogens; Tretinoin; Valproic Acid

Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar disorder, and have been shown to have neuroprotective properties in vivo and in vitro. A recent study demonstrated that combined treatment with lithium and VPA elicits synergistic neuroprotective effects against glutamate excitotoxicity in cultured brain neurons, and the synergy involves potentiated inhibition of glycogen synthase kinase-3 (GSK-3) activity through enhanced GSK-3 serine phosphorylation [Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM (2008) Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J Neurosci 28:2576-2588]. We therefore investigated the effects of lithium and VPA cotreatment on the disease symptom onset, survival time and neurological deficits in cooper zinc superoxide dismutase (SOD1) G93A mutant mice, a commonly used mouse model of amyotrophic lateral sclerosis (ALS). The G93A ALS mice received twice daily i.p. injections with LiCl (60 mg/kg), VPA (300 mg/kg) or lithium plus VPA, starting from the 30(th) day after birth and continuing until death. We found that combined treatment with lithium and VPA produced a greater and more consistent effect in delaying the onset of disease symptoms, prolonging the lifespan and decreasing the neurological deficit scores, compared with the results of monotreatment with lithium or VPA. Moreover, lithium in conjunction with VPA was more effective than lithium or VPA alone in enhancing the immunostaining of phospho-GSK-3beta(Ser9) in brain and lumbar spinal cord sections. To our knowledge, this is the first demonstration of enhanced neuroprotection by a combinatorial approach using mood stabilizers in a mouse ALS model. Our results suggest that clinical trials using lithium and VPA in combination for ALS patients are a rational strategy.

Topics: Adjuvants, Immunologic; Age Factors; Amyotrophic Lateral Sclerosis; Animals; Anticonvulsants; Behavior, Animal; Disease Models, Animal; Drug Therapy, Combination; Glycogen Synthase Kinase 3; Hindlimb Suspension; Humans; Lithium Chloride; Mice; Mice, Transgenic; Motor Activity; Muscle Strength; Mutation; Nervous System Diseases; Psychomotor Performance; Reflex; Rotarod Performance Test; Superoxide Dismutase; Survival Analysis; Valproic Acid