Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.
 ...
PMID:Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases. 2227 Dec 59

Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.
 ...
PMID:Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles. 2236 87

High-frequency deep brain stimulation (HF-DBS) has become a widely used therapeutic method in the field of movement disorders for the treatment of Parkinson's disease, essential tremor or dystonia. New targets and indications are under evaluation in several other conditions such as cluster headache, obesity, epilepsy or psychiatric diseases (depression, OCD). However, the mechanisms of action of HF-DBS remain poorly understood. Herein we present a review of the literature and our current view of the question. The first part deals with the effects of stimulation itself on the different parts of the neuron and tries to answer the question of what is actually stimulated by DBS (cell bodies, dendrites or axons). The second part is devoted to the ortho- and antidromic effects of the stimulation. The third part more specifically focuses on the case of subthalamic nucleus stimulation. The target axons in the subthalamic area are discussed in the light of recent optogenetic studies. In conclusion, HF-DBS leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity (both ortho and antidromically). Which effects are relevant to the therapeutic effects of DBS is still unclear. Further investigations are required especially regarding the corticosubthalamic pathways.
 ...
PMID:[Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts]. 2246 40

The therapeutic use of botulinum toxin Type A has followed a novel and unanticipated pathway of applications, from its initial application by Scott to paralyze the extraocular muscles of the eyes to correct strabismus. In the late 1970s, Scott formed a company, called Oculinum Inc, to make botulinum toxin Type A available for this ophthalmic application. From this modest and limited beginning, it has found use for treatment of a plethora of cosmetic, neuromuscular, and skeletal disabilities, including cervical dystonia, blepharospasm, and temporary improvement in the appearance of moderate to severe glabellar lines. Botulinum toxin Type A is now being used as therapy in voiding disorders, migraine and tension-type headache, writer's cramp, and laryngeal muscle hyperactivity syndromes. It has reduced the spasm and pain associated with perianal fissures. It has found application in the reduction of glandular function in severe primary axillary hyperhidrosis and sialorrhea. Additional applications are being studied in the area of pain management based on its apparent ability to inhibit neuropeptide release from nociceptors.
 ...
PMID:Application of botulinum toxin to clinical therapy: advances and cautions. 2248 7

Botulinum neurotoxin type-A (BoNT-A) is clinically used for patients with pain disorders and dystonia. The precise mechanism whereby BoNT-A controls pain remains elusive. Here, we studied how BoNT-A affects the expression of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a cation channel critically implicated in nociception, in the trigeminal system. Histological studies revealed that subcutaneous BoNT-A injection (0.25, 0.5, or 5 ng/kg) into the face targeted the ophthalmic division of trigeminal ganglion (TG) neurons and decreased TRPV1-immunoreactive neurons in the TG and TRPV1-immunoreactive fibers in rat trigeminal terminals. Of note, TG neurons that received projections from the dura mater, a principal site of headache generation, had reduced TRPV1 expression. BoNT-A-induced cleavage of SNAP25 (synaptosomal-associated protein of 25-kDa) in the TG became obvious 2 days after BoNT-A administration and persisted for at least 14 days. Quantitative real-time RT-PCR (reverse transcription-polymerase chain reaction) data indicated that the TRPV1-decreasing effects of BoNT-A were not mediated by transcriptional downregulation. By employing a surface protein biotin-labeling assay, we demonstrated that BoNT-A inhibited TRPV1 trafficking to the plasma membrane in primary TG neurons. Moreover, Y200F-mutated TRPV1, which is incapable of trafficking to the plasma membrane, was expressed in PC12 cells by transfection, and pharmacological studies revealed that TRPV1 in the cytoplasm was more predisposed to proteasome-mediated proteolysis than plasma membrane-located TRPV1. We conclude that the mechanism by which BoNT-A reduces TRPV1 expression involves the inhibition of TRPV1 plasma membrane trafficking and proteasome-mediated degradation in the cytoplasm. This paradigm seems to explain how BoNT-A alleviates TRPV1-mediated pain. Our data reveal a likely molecular mechanism whereby BoNT-A treatment reduces TRPV1 expression in the trigeminal system and provide important clues to novel therapeutic measures for ameliorating craniofacial pain.
 ...
PMID:Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A. 2282 Jan 41

Despite the common belief that multiple sclerosis (MS) is a painless disease, several studies contradict this. There are a significant number of MS patients who actually suffer from painful conditions such as central and peripheral neuropathy, migraines, trigeminal neuralgia, painful tonic spasms, complex regional pain syndrome, glossopharyngeal neuralgia, and transverse myelitis. In addition, MS relapses are usually painful with many patients complaining of paroxysmal dystonia and neuropathic pain during these episodes. Additionally, treatments for MS such as use of beta-interferons may be associated with headache and pain at the injection site. The pathophysiology of pain in MS is poorly understood, but may be related to the development of demyelinating lesions involving certain neuroanatomic pathways such as the spinothalamic tract. Management of pain in MS patients is a therapeutic challenge for clinicians. Currently, various pharmacological agents such as antiepielptics, non-steroidal anti-inflammatory agents, and even corticosteroids are used to suppress various painful conditions associated with MS. Non-pharmacological procedures such as massage therapy have also been used in the treatment of MS patients. The authors present a review of recent findings in pathophysiology and management of pain in MS patients.
 ...
PMID:Multiple sclerosis and pain. 2290 89

Aripiprazole is an atypical antipsychotic medication that is a partial dopamine D(2) and serotonin 5-hydroxytryptamine (1A) receptor agonist and 5-hydroxytryptamine (2A) receptor antagonist. It has a safer profile compared to other antipsychotic medications with regard to its effect on weight, glucose tolerance, prolactin level, and cardiac conduction. The common neurological adverse effects include headache, agitation, insomnia, sleepiness, and extrapyramidal symptoms. Seizures have not been reported in the pediatric population and only twice in adult patients. Here, we report a case of a healthy 3-year-old child who experienced prolonged lethargy, dystonia, and 2 witnessed seizures after incidental ingestion of 30 mg of aripiprazole. To our knowledge, this is the first reported case of aripiprazole-induced seizures in a child.
 ...
PMID:Aripiprazole-induced seizure in a 3-year-old child: a case report and literature review. 2333 73

At present, botulinum toxin (BT) is one of the most fundamental available drugs in Neurology, only comparable with levodopa. BT is currently used in those entities characterized by excessive muscle contraction, including dystonia and spasticity. In addition, BT has been used to control pain associated with increased muscle contraction in dystonia and spasticity, but also is useful to control chronic pain not associated with muscle contraction, such as chronic daily headache. Finally, BT is useful in sialorrhoea and bruxism. The mechanism of action is complex, mainly acting on terminal neuromuscular junction, but also exhibiting analgesic properties, probably through inhibition of pain neurotransmitters release.
...
PMID:[Applications of botulinum toxin in Neurology]. 2343 66

Botulinum toxin (Botox) is an exotoxin produced from Clostridium botulinum. It works by blocking the release of acetylcholine from the cholinergic nerve end plates leading to inactivity of the muscles or glands innervated. Botox is best known for its beneficial role in facial aesthetics but recent literature has highlighted its usage in multiple non-cosmetic medical and surgical conditions. This article reviews the current evidence pertaining to Botox use in the head and neck. A literature review was conducted using The Cochrane Controlled Trials Register, Medline and EMBASE databases limited to English Language articles published from 1980 to 2012. The findings suggest that there is level 1 evidence supporting the efficacy of Botox in the treatment of spasmodic dysphonia, essential voice tremor, headache, cervical dystonia, masticatory myalgia, sialorrhoea, temporomandibular joint disorders, bruxism, blepharospasm, hemifacial spasm and rhinitis. For chronic neck pain there is level 1 evidence to show that Botox is ineffective. Level 2 evidence exists for vocal tics, trigeminal neuralgia, dysphagia and post-laryngectomy oesophageal speech. For stuttering, 'first bite syndrome', facial nerve paresis, Frey's syndrome, oromandibular dystonia and palatal/stapedial myoclonus the evidence is level 4. Thus, the literature highlights a therapeutic role for Botox in a wide range of non-cosmetic conditions pertaining to the head and neck (mainly level 1 evidence). With ongoing research, the spectrum of clinical applications and number of people receiving Botox will no doubt increase. Botox appears to justify its title as 'the poison that heals'.
 ...
PMID:An evidence-based review of botulinum toxin (Botox) applications in non-cosmetic head and neck conditions. 2347 31

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.
 ...
PMID:Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. 2375 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>