ABSTRACT
In 2011, new oral anticoagulants for atrial fibrillation are available and the ABCD3-I score predicting stroke after TIA updates the ABCD2 score. New McDonald criteria allow faster MS diagnosis and the first oral treatment (fingolimod) for MS can be prescribed. A new anti-antiepileptic drug (retigabine) is available and sodium valproate has long term neurological adverse effects after in utero exposure. Among Parkinson disease treatments, deep brain stimulation is extending applications and dopamine agonists with extended release are as efficient and well tolerated as standard forms at long term scale. Monoclonal antibodies and immunosuppressant agents are proposed as good alternatives in the treatment of chronic dysimmune polyneuropathies. Gene therapy for the treatment of genetic myopathies is progressing.
Subject(s)
Atrial Fibrillation , Epilepsy , Ischemic Attack, Transient , Multiple Sclerosis , Muscular Diseases , Parkinson Disease , Polyneuropathies , Antibodies, Monoclonal/therapeutic use , Anticonvulsants/therapeutic use , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Carbamates/therapeutic use , Chronic Disease , Deep Brain Stimulation , Dopamine Agonists/therapeutic use , Epilepsy/diagnosis , Epilepsy/drug therapy , Fingolimod Hydrochloride , Genetic Therapy/methods , Humans , Immunosuppressive Agents/therapeutic use , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/etiology , Ischemic Attack, Transient/prevention & control , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy , Muscular Diseases/diagnosis , Muscular Diseases/genetics , Muscular Diseases/therapy , Neurology/trends , Parkinson Disease/diagnosis , Parkinson Disease/drug therapy , Phenylenediamines/therapeutic use , Polyneuropathies/diagnosis , Polyneuropathies/drug therapy , Propylene Glycols/therapeutic use , Sphingosine/analogs & derivatives , Sphingosine/therapeutic use , Stroke/drug therapy , Treatment Outcome , Valproic Acid/therapeutic useABSTRACT
Konzo is an upper motor neuron disease characterized by sudden-onset and irreversible spastic paraparesis occurring in nutritionally compromised people. It is associated with consumption of insufficiently processed cyanogenic-toxic cassava. Cassava, the main caloric source in the Democratic Republic of Congo, has been safely consumed for decades in the Eastern Province of South-Kivu. However, in the context of long-lasting war and violent conflicts, cases of spastic paraparesis resembling konzo appeared in a populous area (Burhinyi). Two field surveys (2003 and 2005) identified 41 subjects meeting clinical criteria of konzo and suffering from (chronic) malnutrition. Their urinary thiocyanate concentrations (median 129, range 20-688, SD 146 µg/L), and cyanogen levels (median 20 ppm, range 5-300 ppm, SD 73 ppm) in cassava roots from their household stocks were high. The source of cyanogenic-toxicity was unprocessed fresh cassava roots during harvest period, but probably also insufficiently processed roots. This first report of konzo in South-Kivu concludes that occurrence of konzo was triggered by food shortages because of the longstanding state of insecurity. Contributory factors included the introduction of new varieties of (bitter) cassava, but konzo may actually be caused by a combination of factors that are yet to be understood.
Subject(s)
Manihot/chemistry , Manihot/poisoning , Motor Neuron Disease/epidemiology , Paraparesis, Spastic/epidemiology , Thiocyanates/urine , Adolescent , Adult , Child , Child, Preschool , Cyanides/poisoning , Democratic Republic of the Congo/epidemiology , Female , Foodborne Diseases/complications , Foodborne Diseases/epidemiology , Humans , Malnutrition/complications , Motor Neuron Disease/etiology , Nitriles/analysis , Paraparesis, Spastic/complications , Plant Roots/chemistry , Plant Roots/poisoning , Young AdultABSTRACT
Plasma membrane chloride (Cl(-)) pathways play an important role in neuronal physiology. Here, we investigated the role of NKCC1 cotransporters (a secondary active Cl(-) uptake mechanism) in Cl(-) handling in cultured rat dorsal root ganglion neurons (DRGNs) and motor neurons (MNs) derived from fetal stage embryonic day 14. Gramicidin-perforated patch-clamp recordings revealed that DRGNs accumulate intracellular Cl(-) through a bumetanide- and Na(+)-sensitive mechanism, indicative of the functional expression of NKCC1. Western blotting confirmed the expression of NKCC1 in both DRGNs and MNs, but immunocytochemistry experiments showed a restricted expression in dendrites of MNs, which contrasts with a homogeneous expression in DRGNs. Both MNs and DRGNs could be readily loaded with or depleted of Cl(-) during GABA(A) receptor activation at depolarizing or hyperpolarizing membrane potentials. After loading, the rate of recovery to the resting Cl(-) concentration (i.e., [Cl(-)](i) decrease) was similar in both cell types and was unaffected by lowering the extracellular Na(+) concentration. In contrast, the recovery on depletion (i.e., [Cl(-)](i) increase) was significantly faster in DRGNs in control conditions but not in low extracellular Na(+). The experimental observations could be reproduced by a mathematical model for intracellular Cl(-) kinetics, in which DRGNs show higher NKCC1 activity and smaller Cl(-)-handling volume than MNs. On the basis of these results, we conclude that embryonic DRGNs show a higher somatic functional expression of NKCC1 than embryonic MNs. The high NKCC1 activity in DRGNs is important for maintaining high [Cl(-)](i), whereas lower NKCC1 activity in MNs allows large [Cl(-)](i) variations during neuronal activity.
Subject(s)
Chlorides/metabolism , Ganglia, Spinal/metabolism , Motor Neurons/metabolism , Receptors, GABA-A/metabolism , Sodium-Potassium-Chloride Symporters/physiology , Animals , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bumetanide/metabolism , Bumetanide/pharmacology , Cells, Cultured , Electrophysiology , Embryo, Mammalian , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Ganglia, Spinal/embryology , Gramicidin/metabolism , Gramicidin/pharmacology , Immunohistochemistry , Kinetics , Models, Statistical , Motor Neurons/cytology , Motor Neurons/drug effects , Motor Neurons/physiology , Patch-Clamp Techniques , Rats , Rats, Inbred Strains , Receptors, GABA/metabolism , Receptors, GABA-A/physiology , Sodium Potassium Chloride Symporter Inhibitors , Sodium-Potassium-Chloride Symporters/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
Despite the recognized role of traditional healers in helping patients with mental health problems, there is a need for modern mental healthcare facilities in Africa. When made available, these are used by the local population, but less by those at remote locations. Data from the SOSAME centre indicate the high prevalence of mental diseases, especially in urban population and during the active decades of life. To decrease the burden imposed on mental health institutions by patients consulting for non-mental problems, it is desirable to integrate these institutions with the other components of the healthcare system.
