Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large number of opioids and nonopioids have been administered epidurally and intrathecally in the hope of providing segmental analgesia without serious adverse effects. However, neurotoxicity data are generally unavailable for many of these drugs. The present study evaluated the behavioral, motor, electroencephalographic, and histopathologic changes following intrathecal injection of large and small doses of butorphanol, sufentanil, and nalbuphine in sheep. Thirty-two sheep (20-32 kg) were anesthetized and catheters placed intrathecally after hemilaminectomy. The large doses of butorphanol, sufentanil and nalbuphine were 0.375 mg/kg (4.4-5.2 ml), 7.5 micrograms/kg (3.6-4.8 ml) and 0.75 mg/kg (1.5-2.4 ml), and the small doses were 0.075 mg/kg (0.9-1.1 ml), 1.5 micrograms/kg (0.7-0.9 ml) and 0.15 mg/kg (0.38-0.5 ml), respectively. The opioids were administered intrathecally every 6 h for 3 days and the above-mentioned parameters studied. Five sheep received intrathecal saline (1.1 or 5.2 ml) and served as controls. Histopathologic changes were evaluated by a neuropathologist blinded to the study protocol. Irrespective of dose, intrathecal injection of butorphanol was associated with severe behavioral responses such as agitation, rigidity, vocalization, and restlessness, as well as prolonged or irreversible hindlimb paralysis. Electroencephalography showed increased cortical activity or seizure activity. One sheep died because of severe respiratory depression that did not respond to naloxone. Spinal cord histologic changes consisted of suppurative meningitis and myelitis as well as neuronal changes such as spongiosis and chromatolysis. Large doses of intrathecal sufentanil were associated with similar though somewhat less severe responses. The behavioral and motor changes following the small dose of intrathecal sufentanil were of mild to moderate nature. Following intrathecal nalbuphine, the above-mentioned changes were similar to those seen in control animals. We conclude that butorphanol in doses of 0.075 and 0.375 mg/kg intrathecally and sufentanil 7.5 micrograms/kg intrathecally are neurotoxic in sheep.
 ...
PMID:Behavioral and histopathologic effects following intrathecal administration of butorphanol, sufentanil, and nalbuphine in sheep. 138 69

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.
 ...
PMID:Chronic intrathecal baclofen administration for control of severe spasticity. 230 74

Thrombosis, thrombocytopenia, recurrent fetal loss and a variety of non-thrombotic neurological disorders have all been associated with antiphospholipid antibodies (aPL). Cerebral ischemia associated with aPL is the most common arterial thrombotic manifestation. Depression, cognitive dysfunction, depression and psychosis have all been associated with aPL. The presumed pathophysiologic mechanism underlying these manifestations is thought to be a result of cerebral ischemia in some, but not all cases. Seizures, chorea and transverse myelitis all appear to be associated with aPL. An interaction between aPL and central nervous system cellular elements rather than aPL-associated thrombosis seems to be a more plausible mechanism for these clinical manifestations. Migraine on the other hand, does not appear to be associated with aPL in either lupus or non-lupus populations. Neuroimaging studies show an increased frequency of brain abnormalities in patients with aPL, but none appear to be specific. The best treatment strategy for preventing neurological manifestations of aPL is not fully defined. For thrombotic manifestations, both antiplatelet and anticoagulant therapies have been suggested. In some patients, immunosuppressant therapy has been used. For non-thrombotic manifestations, some combination of immunosuppressant therapy and symptomatic treatment may be warranted.
 ...
PMID:Neurological manifestations of antiphospholipid antibody syndrome. 981 77

Japanese encephalitis (JE) vaccine has been used for childhood immunization programmes in Asia since the 1960s. Also, travellers from other parts of the world have been vaccinated before travelling to Asian countries. Some JE vaccines are produced from infected mouse brains and contain small amounts of myelin basic protein. Neurological side effects in larger vaccine trials in Asia have been reported in 1-2.3 per million vaccinees. Statens Serum Institut is the only distributor of JE vaccine in Denmark, delivering 384 000 doses from 1983-96. In 1996, evaluation of initial symptoms and findings in 10 adult travellers from Denmark, who developed moderate-severe neurological symptoms within a few weeks of JE vaccination, was performed as well as follow-up magnetic resonance imaging (MRI) and clinical neurological examination. Three patients initially had symptoms varying from severe encephalitis-like illness to paraesthesia, double vision or parkinsonian gait disturbance. MRI showed severe atrophy of the corpus callosum with altered signal intensity indicating gliosis in one patient, another patient had several hyperintense spots located periventricularly in the white matter, while a third patient had spots with increased signals in the pons, the right substantia nigra and the occipital region. Acute disseminated encephalomyelitis (ADEM) is a possible explanation for these MRI changes, although multiple sclerosis is an alternative diagnosis in one or two of the patients. Another three patients had long-lasting headache, concentration difficulty or intellectual reduction. One man had afebrile convulsions, another gait instability and depression and one parkinsonism. A woman developed myelitis. If these findings are due to JE vaccination the frequency of neurological reactions to the vaccine is considerably higher than previously reported and in the future any minor neurological complaints occurring shortly after vaccination should lead to neurological examination and acute MRI scan should be considered. Copyright 1998 Lippincott Williams & Wilkins
 ...
PMID:Neurological complications to vaccination against Japanese encephalitis. 1021 Aug 77

The treatment of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) can be difficult and complex owing to the variety of nervous system manifestations that can occur, which include peripheral nerve disease, headaches, seizures, cerebrovascular disease, chorea, transverse myelitis, and psychiatric and cognitive disorders. Many of these manifestations can result from metabolic abnormalities or infection or as side effects of medications. Thus, in any patient with suspected NPSLE, it is crucial to exclude secondary causes of the presenting symptoms before assuming that they are due to NPSLE. It is especially important to exclude infection because this is a common cause of both morbidity and mortality in patients with systemic lupus erythematosus (SLE). Symptoms such as anxiety and depression may or may not be related to disease activity. Treatment decisions are based on accurate diagnosis of the specific NPSLE manifestation, which is usually made using tools such as brain imaging, electroencephalography, cerebrospinal fluid analysis, nerve conduction studies, or special serologic tests (eg, determination of antiphospholipid or antiribosomal P antibody levels). It is also important to assess the degree of other SLE- mediated systemic disease activity in a patient with neurologic manifestations to determine if activation of systemic disease activity is also occurring. This is done by measuring complement levels, anti-double-stranded DNA levels, complete blood count, and urinalysis. For some NPSLE manifestations (eg, infrequent seizures, headaches, depression, anxiety, or peripheral neuropathy) that appear without activation of systemic disease, symptomatic treatment is appropriate. For others (eg, psychosis, delirium, or transverse myelopathy without other obvious cause), treatment with high-dose glucocorticoids with or without cyclophosphamide is appropriate whether there is evidence of other systemic disease activity or not. In general, the activity and severity of the leading organ manifestations dictate pharmacologic treatment.
 ...
PMID:Neuropsychiatric Systemic Lupus Erythematosus. 1109 72

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 +/- 15 years, mean disease duration 8 +/- 11 years) were recruited through advertisements. All participants adhered to a gluten-free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten-free diet.
 ...
PMID:Neurological symptoms in patients with biopsy proven celiac disease. 2043 47

Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection, other neurologic complications may occur, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panicc attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome. We describe here a patient with a triad of unusual symptoms in chronic LNB including tremor, seizures and psychosis. Standardized medical interview, neurologic examination, neuroimaging, serum and CSF serology as well as EEG and EMNG evaluation were performed. The patient was treated with intravenous ceftriaxone and doxycycline and responded with rapid clinical and functional improvement.Newertheless, he suffered from multiple systemic and neurologic sequelas that influenced his daily activities in post treatment period. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating diagnosis, early treatment and the uncertainties concerning the sequelae after treatment. In patients with non-specific long lasting symptoms in the absence of overt clinical signs suggesting CNS involvement, routine treatment with i.v. ceftriaxone is not to be encouraged.
 ...
PMID:Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB). 2164 54

Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in childhood. Childhood multiple sclerosis has a relapsing-remitting disease course. The first attack, or "acquired demyelinating syndrome," consists of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and monofocal or polyfocal neurological deficits. The diagnosis of multiple sclerosis necessitates the clinical or magnetic resonance imaging confirmation of dissemination in space and time and exclusion of other disorders. The morbidity of childhood multiple sclerosis is significant; within the first 2 years from onset, 30% of children have significant cognitive impairment, 50% show signs of depression, and 75% are fatigued. The relapse rate in children with multiple sclerosis is higher than in adult-onset disease. Following acute treatment, recovery after the first attacks is usually excellent, but patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onset multiple sclerosis.
 ...
PMID:Pediatric multiple sclerosis. 2291 72

A 4-year-old male Labrador Retriever dog was presented with a 10-day history of tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber destruction together with mixed inflammatory infiltration was observed in the spinal nerves. Cervical spinal cord sections showed multifocal, diffuse granulomatous inflammation in the white matter. In the brain, perivascular infiltrates were observed in some areas together with subtle pallor of the parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid plexuses. The current study describes the presence of Leishmania amastigotes in nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis, suggesting a likely route by which L. infantum amastigotes reach and affect the central nervous system parenchyma.
 ...
PMID:Leishmania amastigotes in the central nervous system of a naturally infected dog. 2316 83

Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO). While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST) following the protocol of the German Research Network on Neuropathic Pain (DFNS). Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11) suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG). These data emphasize the high prevalence of neuropathic pain and hyperalgesia in patients with NMO. The degree of mechanical hyperalgesia reflecting central sensitization of nociceptive pathways seems to be controlled by the major brain endocannabinoid 2-AG.
...
PMID:The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica. 2395 Nov 76


1 2 Next >>