Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-five patients with Wilson's disease (WD) were prospectively studied: 27 had neurological deficits, 12 hepatic signs, and 6 were asymptomatic. Kayser-Fleischer rings occurred in 23 of the neurological patients and in only 4 of the hepatic patients. Neurological features were extremely variable with respect to frequency and severity. Most frequent were dysdiadochokinesis (25 patients), dysarthria (23), bradykinesia (17), and posture tremor (14). Fifteen, mainly long-term treated patients, presented with rather discrete neurological abnormalities which predominantly consisted of dysarthria and various forms of tremor. Eight patients had a parkinsonian type of neurological WD associated with signs of an organic mood syndrome. Three patients were predominantly hyperkinetic, presenting with dystonic and choreatic movements. In 1 patient, ataxia was the predominant neurological feature. There was a clear-cut correlation between the severity of neurological impairment and the restriction in functional capacity. Nine patients were not able to engage in salaried employment or were retired. Psychiatric symptoms and behavioural disorders were common, varying from mild personality and psychological disturbances to severe psychiatric illness resembling psychotic disorders and major depressive syndromes. Significant mental deterioration was not found in the patients. Disturbances of mood were observed in 12 patients, all of whom had neurological abnormalities. There was a history of an attempted suicide in 7 patients, and a history of an organic delusional syndrome in 3.
 ...
PMID:Neurological and neuropsychiatric spectrum of Wilson's disease: a prospective study of 45 cases. 191 12

The case of a childhood form of Huntington's disease in a 12-years-old girl is reported. The patient suffered from severe psychosis, progressive difficulties in speaking, and mental deterioration. Her father committed suicide due to Huntington's disease when the patient was eight years old. Neurological examination revealed nothing but speaking difficulties. She had no signs or symptoms of involuntary movements, muscular rigidity or ataxia. SPECT-scanning showed a picture similar to that seen in adult patients with Huntington's disease. The difficulties in diagnosing Huntington's disease in children are discussed, and the necessity of the child psychiatric expertise is emphasized.
 ...
PMID:[Early onset of Huntington disease]. 868 96

Molecular analysis of five Brazilian families, including eight patients presenting with nonclassic Tay-Sachs disease, was performed to identify frequent causative mutations and their correlation with clinical course. Three patients were affected by the B1 subacute variant and were shown to carry the R178H mutation (the DN allele), which is also common among Portuguese patients. Two of them were compound heterozygotes, whereas the third presented with the mutation in both alleles. Since Brazil was a Portuguese colony for over two centuries, common ancestry might be the probable explanation. The fourth patient presented with a juvenile phenotype and carries the R499H mutation, which has been reported only once worldwide and is associated with residual enzyme activity, responsible for a slower clinical course. The fifth family, of an Ashkenazi Jewish background, showed an extensive intrafamilial clinical variability among three affected sibs presenting with muscle atrophy, ataxia, and psychiatric symptoms. They were first diagnosed as having atypical spinal muscular atrophy and, subsequently, spinocerebellar ataxia, but, recently, the diagnosis of late-onset Tay-Sachs disease was confirmed based on reduced plasma hexosaminidase A activity and the G269S/InsTATC1278 genotype. It is therefore highly recommended to test patients with a similar clinical history for Tay-Sachs disease. In the same family, one first cousin committed suicide at the age of 24 years, presenting with a clinical phenotype that suggested an undiagnosed case and highlighting the effect of the intrafamilial clinical variability in delaying a prompt diagnosis. It is now recognized that his parents are, in fact, a carrier couple. Additionally, another relative had been previously identified as a heterozygote in a Tay-Sachs disease screening program, but the information was not shared among the family. Since this information might anticipate diagnosis and genetic counseling, it is advisable that heterozygote screening programs encourage families to share genetic information.
 ...
PMID:Diagnosis and molecular characterization of non-classic forms of Tay-Sachs disease in Brazil. 1694 47

Due to its chronic and fluctuating time course, multiple sclerosis (MS), thus far, has not been regarded as a focus of palliative care. However, sometimes we are confronted with severely affected MS patients, who suffer from complex medical, physical and psychosocial problems, which are not fully covered by the current health care services. We present two cases of severely affected MS patients we saw in our outpatient MS clinic, and who, we believe, are candidates for palliative care. The first patient, with primary chronic progressive (pcP) MS for many years (Expanded Disability Status Scale (EDSS): 8.0) presented with complex painful dysaesthesias and a depressive syndrome. He refused any treatment, and finally committed suicide with the help of a euthanasia group in Switzerland. The second patient was also severely affected by a secondary chronic progressive (scP) MS (EDSS: 9.0) and was finally admitted to our palliative care unit due to a complex pain syndrome associated with panic attacks and anxiety. She spent three weeks on the palliative care unit and her symptoms improved gradually after changing and optimising her pain medication. The patient was discharged with home care and is seen regularly on the palliative care unit. Additionally, as a first step, a questionnaire was sent to 53 German MS specialists regarding their general view on the needs for palliative care in MS. Our two cases and the results of the questionnaire demonstrated that MS patients and their caregivers are confronted with a variety of symptoms which are difficult to treat, and are a cause of great suffering for the patients, including ataxia, depression and fatigue. The data of the questionnaire also showed that neurologists usually do not deal with end-of-life care issues in MS.More research is needed to define the role of palliative care in MS and establish appropriate interventions to improve the quality of life in advanced stage MS patients and their relatives.
 ...
PMID:Palliative care in patients with severe multiple sclerosis: two case reports and a survey among German MS neurologists. 1734 59

Programmed cell death is a term which refers to a genetic decision of self-killing or suicide of a cell. Programmed cell death is not restricted to multicellular organisms and was described in a wide range of unicellular eukaryotes, indicating phylogenetically conserved functions, that participate in an adaptive response to cellular stress. Here we review and discuss our observations recently published in the EMBO Journal,(1) that non-dividing fission yeast, Schizosaccharomyces pombe, exhibits a DNA damage response leading to cell death. We found that Tdp1 protects quiescent S. pombe cells against oxidative DNA damage. Tdp1 is a well-conserved tyrosyl-DNA phosphodiesterase required for single-strand break DNA repair, the mutation of Tdp1 is responsible for the recessively inherited syndrome spinocerebellar ataxia with axonal neuropathy (SCAN1) in humans. We found that tdp1 mutant yeast cells grow, as well as the wild-type cells, during the vegetative state, but progressively die in the quiescent state. We showed that, in the absence of Tdp1, the accumulation of unrepaired oxidative DNA damage triggers a genetic response, leading to checkpoint-dependent (ATM/ATR) nuclear DNA degradation, reminiscent of apoptosis. Our results indicate that the reactive oxygen species (ROS) produced during mitochondrial respiration are the main DNA damaging agents in the physiological quiescent state.
 ...
PMID:Unrepaired oxidative DNA damage induces an ATR/ATM apoptotic-like response in quiescent fission yeast. 1957 71

Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of transient depolarizing currents and play a critical role in the electrical signaling between neurons. A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family. Heterozygous mutation carriers displayed a range of phenotypes, including ataxia, cognitive deficits, and emotional instability. A possible role for SCN8A was also proposed in studies examining the genetic basis of attempted suicide and bipolar disorder. In addition, mice with a Scn8a loss-of-function mutation (Scn8a(med-Tg/+)) show altered anxiety and depression-like phenotypes. Because psychiatric abnormalities are often associated with altered sleep and hormonal patterns, we evaluated heterozygous Scn8a(med-jo/+) mutants for alterations in sleep-wake architecture, diurnal corticosterone levels, and behavior. Compared with their wild-type littermates, Scn8a(med-jo/+) mutants experience more non-rapid eye movement (non-REM) sleep, a chronic impairment of REM sleep generation and quantity, and a lowered and flattened diurnal rhythm of corticosterone levels. No robust differences were observed between mutants and wild-type littermates in locomotor activity or in behavioral paradigms that evaluate anxiety or depression-like phenotypes; however, Scn8a(med-jo/+) mutants did show enhanced spatial memory. This study extends the spectrum of phenotypes associated with mutations in Scn8a and suggests a novel role for altered sodium channel function in human sleep disorders.
 ...
PMID:Dysfunction of the Scn8a voltage-gated sodium channel alters sleep architecture, reduces diurnal corticosterone levels, and enhances spatial memory. 2035 42

Alcohol dependence is a severe, chronic illness. Even the best-assessed drugs used to maintain abstinence are poorly effective. Some patients remain dependent after several treatment attempts. Baclofen has been tested for its capacity to reduce craving for alcohol. We reviewed the data available as of early 2013, using the standard Prescrire methodology, in order to assess the harm-benefit balance of baclofen in maintaining abstinence or moderation in alcohol-dependent patients. Two double-blind, randomised, placebo-controlled trials conducted by the same team tested baclofen 30 mg/day in 123 alcohol-dependent patients referred to alcohol treatment centres. After 1 or 3 months of followup, more patients remained abstinent in the baclofen group than in the placebo group. In another double-blind, randomised trial, baclofen 30 mg/day was not more effective than placebo in 80 alcohol-dependent patients recruited through advertisements, many of whom were seeking treatment for the first time. Three uncontrolled retrospective series reported the results obtained in 300 alcohol-dependent patients, most of whom were in treatment failure. They were treated with high, escalating doses of baclofen (on average about 150 mg per day, up to 400 mg per day) with the intention of reducing their craving for alcohol. After 3 to 24 months of follow-up, about half of the patients reported moderate or zero alcohol consumption. At moderate doses, baclofen has been used since the 1970s in the treatment of certain forms of muscle spasticity. The main adverse effects reported in this setting were drowsiness (especially early during treatment) and various neuropsychiatric disorders such as dizziness, euphoria, depression, headache, paraesthesias, speech disorders, ataxia and insomnia. The adverse effects of high-dose baclofen are mainly based on monitoring of hundreds of alcohol-dependent patients, 69 reports to French pharmacovigilance centres in 2011, and cases of overdose or accidental ingestion reported to French poison control centres. Confusion and mania were reported, and coma occurred with doses of 200 mg or more. Some data point to an increased risk of suicide. In practice, in early 2013, more data are needed on the efficacy and adverse effects of baclofen in alcohol dependence, compared with other options. Patients who have received thorough, well-balanced information, and decide to try baclofen as a last resort should be included in comparative clinical studies.
 ...
PMID:Baclofen and severe alcohol dependence: an uncertain harm-benefit balance as of early 2013. 2417 Dec 18

The practice of inhaling liquefied petroleum gas (LPG) to commit suicide is uncommon and almost exclusively a prerogative of the prison population. Numerous cases of sudden deaths caused by intentional propane and/or butane inhalation have been described, but these cases survived and a description of the consequences is very rare. We describe a prisoner who survived after voluntary inhalation of LPG, and who developed ataxia, Parkinsonism, and dystonia. Brain MRI showed bilateral hyperintensity in the basal ganglia and in the cerebellar hemispheres. The clinical evolution and the MRI abnormalities are similar to those described in cases of poisoning by CO where the mechanism of brain injury is related to histotoxic hypoxia. We believe that LPG, considered until now a mixture of gas with low neurotoxic power, may have caused direct toxic damage to the brain, mediated by a mechanism of hypoxia, such as in CO intoxication.
...
PMID:Ataxia with Parkinsonism and dystonia after intentional inhalation of liquefied petroleum gas. 2600 50

In the United States, benzodiazepine medication use is the secondary epidemic to opioid drug use and carries serious consequences as well, even though its use is enabled by well-intended clinicians. Benzodiazepine drugs are intended for short-term use, not to exceed 2 to 4 weeks; yet, it is common for clients to be taking benzodiazepine medications for up to 10 years. In addition to dependence or addiction, adverse effects include depression, emotional blunting, ataxia, aggression, irritability, nervousness, and cognitive impairment. These medications also contribute to increased risk for falls, suicide, overdose fatality, and vehicle crashes. The current article describes the epidemiology of benzodiazepine medication use, patient and prescriber factors that contribute to overuse and misuse, and recommendations for prescribing and deprescribing. [Journal of Psychosocial Nursing and Mental Health Services, 56(6), 11-15.].
 ...
PMID:Benzodiazepine Use: The Underbelly of the Opioid Epidemic. 2987 1