User talk:Z3389806: Difference between revisions

From Embryology
Line 156: Line 156:
| Valproic acid <ref><pubmed>16507108</pubmed></ref>
| Valproic acid <ref><pubmed>16507108</pubmed></ref>
|Depakene Depakote
|Depakene Depakote
| align="left"|renal toxicity <ref><pubmed>8108303</pubmed></ref><ref><pubmed>21868496</pubmed></ref>, hepatoxicity <ref><pubmed>21492891</pubmed></ref>, hemorrhagic pancreatitis, coagulopathies, bone marrow suppression and encephalopathy <ref><pubmed>18201150</pubmed></ref>
| align="center"|renal toxicity <ref><pubmed>8108303</pubmed></ref><ref><pubmed>21868496</pubmed></ref>, hepatoxicity <ref><pubmed>21492891</pubmed></ref>, hemorrhagic pancreatitis, coagulopathies, bone marrow suppression and encephalopathy <ref><pubmed>18201150</pubmed></ref>
|- align="center"  
|- align="center"  
| Lorazepam  
| Lorazepam  
| Ativan
| Ativan
| align="left"|sleepiness <ref><pubmed>4341107</pubmed></ref>, withdrawal symptoms <ref><pubmed>6131080</pubmed></ref>, memory impairment and  confusion <ref><pubmed>3960963</pubmed></ref>
| align="center"|sleepiness <ref><pubmed>4341107</pubmed></ref>, withdrawal symptoms <ref><pubmed>6131080</pubmed></ref>, memory impairment and  confusion <ref><pubmed>3960963</pubmed></ref>
|- align="center"
|- align="center"
| Lamotrigine  
| Lamotrigine  
| Lamictal
| Lamictal
| align="left"|chorea <ref><pubmed>16900938</pubmed></ref>, toxic epidermal necrolysis <ref><pubmed>9061826</pubmed></ref><ref><pubmed>12892003</pubmed></ref> and multiorgan failure <ref><pubmed>19380079</pubmed></ref>
| align="center"|chorea <ref><pubmed>16900938</pubmed></ref>, toxic epidermal necrolysis <ref><pubmed>9061826</pubmed></ref><ref><pubmed>12892003</pubmed></ref> and multiorgan failure <ref><pubmed>19380079</pubmed></ref>
|- align="center"
|- align="center"
| Levetiracetam <ref><pubmed>16340384</pubmed></ref>
| Levetiracetam <ref><pubmed>16340384</pubmed></ref>
| Keppra
| Keppra
| align="left"|somnolence, lethargy <ref><pubmed>18728811</pubmed></ref>, rhinitis, asthenia <ref><pubmed>10908898</pubmed></ref>, headache and dizziness <ref><pubmed>10999557</pubmed></ref>
| align="center"|somnolence, lethargy <ref><pubmed>18728811</pubmed></ref>, rhinitis, asthenia <ref><pubmed>10908898</pubmed></ref>, headache and dizziness <ref><pubmed>10999557</pubmed></ref>
|- align="center"
|- align="center"
| Tetrabenazine <ref><pubmed>16476934</pubmed></ref>
| Tetrabenazine <ref><pubmed>16476934</pubmed></ref>
| Xenazine
| Xenazine
| align="left"|drowsiness,  depression, nausea, worsening of parkinsonism, xerostomia, hypotension <ref><pubmed>19050408</pubmed></ref>
| align="center"|drowsiness,  depression, nausea, worsening of parkinsonism, xerostomia, hypotension <ref><pubmed>19050408</pubmed></ref>
|- align="center"
|- align="center"
| Clonazepam  
| Clonazepam  
|Klonopin Rivotril
|Klonopin Rivotril
| align="left"|drowsiness <ref><pubmed>12390050</pubmed></ref>, depression, disinhibition and sexual dysfunction <ref><pubmed>2889724</pubmed></ref>
| align="center"|drowsiness <ref><pubmed>12390050</pubmed></ref>, depression, disinhibition and sexual dysfunction <ref><pubmed>2889724</pubmed></ref>
|- align="center"
|- align="center"
| Antianxiety drugs  
| Antianxiety drugs  
| Diazepam
| Diazepam
|Valium Antenex
|Valium Antenex
| align="left"|rebound anxiety after withdrawal <ref><pubmed>6145363</pubmed></ref>
| align="center"|rebound anxiety after withdrawal <ref><pubmed>6145363</pubmed></ref>
|- align="center"
|- align="center"
| rowspan="9" style="background:#eeeeff"|Psychiatric disorders
| rowspan="9" style="background:#eeeeff"|Psychiatric disorders
Line 187: Line 187:
| Escitalopram
| Escitalopram
|Lexapro Lexamil Lexam
|Lexapro Lexamil Lexam
| align="left"|insomnia, somnolence, dizziness, sweating, constipation, fatigue <ref>http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-323.pdf_Lexapro_Medr_P1.pdf</ref>, sexual dysfunction <ref><pubmed>16430968</pubmed></ref>, suicidal ideation <ref><pubmed>19832967</pubmed></ref>
| align="center"|insomnia, somnolence, dizziness, sweating, constipation, fatigue <ref>http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-323.pdf_Lexapro_Medr_P1.pdf</ref>, sexual dysfunction <ref><pubmed>16430968</pubmed></ref>, suicidal ideation <ref><pubmed>19832967</pubmed></ref>
|- align="center"
|- align="center"
| Fluoxetine
| Fluoxetine
|Prozac Sarafem Fontex
|Prozac Sarafem Fontex
| align="left"|mania <ref><pubmed>3485926</pubmed></ref>, akathisia <ref><pubmed>2549018</pubmed></ref>, asthenia, tremor, nausea <ref>http://pi.lilly.com/us/prozac.pdf</ref>
| align="center"|mania <ref><pubmed>3485926</pubmed></ref>, akathisia <ref><pubmed>2549018</pubmed></ref>, asthenia, tremor, nausea <ref>http://pi.lilly.com/us/prozac.pdf</ref>
|- align="center"
|- align="center"
| Sertraline  
| Sertraline  
|Zoloft Lustral
|Zoloft Lustral
| align="left"|similar effects to flouxetine and escitalopram: movement disorders and sexual dysfunction <ref><pubmed>8909330</pubmed></ref><ref><pubmed>11229450</pubmed></ref>
| align="center"|similar effects to flouxetine and escitalopram: movement disorders and sexual dysfunction <ref><pubmed>8909330</pubmed></ref><ref><pubmed>11229450</pubmed></ref>
|- align="center"
|- align="center"
| Nortriptyline
| Nortriptyline
|Aventyl Noritren Sensoval Pamelor
|Aventyl Noritren Sensoval Pamelor
| align="left"|suicidal ideation <ref><pubmed>19832967</pubmed></ref>, hepatic failure <ref><pubmed>8848811</pubmed></ref>, dry mouth, sedation, constipation and increased appetite
| align="center"|suicidal ideation <ref><pubmed>19832967</pubmed></ref>, hepatic failure <ref><pubmed>8848811</pubmed></ref>, dry mouth, sedation, constipation and increased appetite
|- align="center"
|- align="center"
| Mirtazapine  
| Mirtazapine  
| Remeron Avanza Zispin
| Remeron Avanza Zispin
| align="left"|dry mouth, sedation, and increases in appetite and body weight <ref><pubmed>11607047</pubmed></ref>, restless legs syndrome (RLS) <ref><pubmed>18756499</pubmed></ref>
| align="center"|dry mouth, sedation, and increases in appetite and body weight <ref><pubmed>11607047</pubmed></ref>, restless legs syndrome (RLS) <ref><pubmed>18756499</pubmed></ref>
|- align="center"
|- align="center"
| rowspan="2"|Antipsychotic drugs
| rowspan="2"|Antipsychotic drugs
| Haloperidol
| Haloperidol
|Haldol Serenase Linton
|Haldol Serenase Linton
| align="left"|acute dystonia, akathisia, parkinsonism <ref><pubmed>17054159</pubmed></ref>, cognitive decline & brain damage <ref><pubmed>18228005</pubmed></ref>
| align="center"|acute dystonia, akathisia, parkinsonism <ref><pubmed>17054159</pubmed></ref>, cognitive decline & brain damage <ref><pubmed>18228005</pubmed></ref>
|- align="center"
|- align="center"
| Clozapine
| Clozapine
|Clozaril Clopine Zaponex
|Clozaril Clopine Zaponex
| align="left"|agranulocytosis <ref><pubmed>8515788</pubmed></ref>, myocarditis <ref><pubmed>17194170</pubmed></ref>, gastrointestinal hypomotility <ref><pubmed>18452342</pubmed></ref>
| align="center"|agranulocytosis <ref><pubmed>8515788</pubmed></ref>, myocarditis <ref><pubmed>17194170</pubmed></ref>, gastrointestinal hypomotility <ref><pubmed>18452342</pubmed></ref>
|- align="center"
|- align="center"
| rowspan="2"|Mood-stabilizing drugs
| rowspan="2"|Mood-stabilizing drugs
| Lithium
| Lithium
| Lithobid
| Lithobid
| align="left"|renal failure <ref><pubmed>19940841</pubmed></ref>, nystagmus <ref><pubmed>12552061</pubmed></ref>, teratogenicity <ref><pubmed>11948561</pubmed></ref>
| align="center"|renal failure <ref><pubmed>19940841</pubmed></ref>, nystagmus <ref><pubmed>12552061</pubmed></ref>, teratogenicity <ref><pubmed>11948561</pubmed></ref>
|- align="center"
|- align="center"
| Carbamazepine
| Carbamazepine
|Tegretol Carbatol Sirtal
|Tegretol Carbatol Sirtal
| align="left"|congenital malformations <ref><pubmed>21127116</pubmed></ref>, pitch perception deficit <ref><pubmed>12581810</pubmed></ref>
| align="center"|congenital malformations <ref><pubmed>21127116</pubmed></ref>, pitch perception deficit <ref><pubmed>12581810</pubmed></ref>
|}
|}
'''Table 3''' ''Symptomatic medications for Huntington's disease''
'''Table 3''' ''Symptomatic medications for Huntington's disease''

Revision as of 06:10, 19 September 2011

History

Huntington's disease has existed since at least the seventeenth century and several physicians provided earlier descriptions of hereditary chorea but without much detail. In 1872, Huntington’s disease was first documented with great details by George Huntington in “On Chorea” [1]. Huntington’s disease was initially known as chorea, derived from the Greek word khoreia which means dancing in unison. George Huntington described the disease as “an heirloom from generations away back in the dim past” as he realized that HD was hereditary. This conclusion was reached when he observed that if one of the parents had the disease, the offspring will inevitably have the disease too. In his paper, “On Chorea”, he described:

"Of its hereditary nature. When either or both the parents have shown manifestations of the disease ..., one or more of the offspring almost invariably suffer from the disease ... But if by any chance these children go through life without it, the thread is broken and the grandchildren and great-grandchildren of the original shakers may rest assured that they are free from the disease.".[2]

Huntington thus was able to explain the precise pattern of inheritance of autosomal dominant disease years before the rediscovery by scientists of Mendelian inheritance.


TIMELINE OF HUNTINGTON'S DISEASE RESEARCH [3]

1872: George Huntington’s paper was published.[4]

1888: Hoffman describes juvenile HD.[5]

1900: Mendel’s work was rediscovered.[6]

1908: Punnett cites HD as autosomal dominant.[7]

1978: Restriction fragment-length polymorphisms (RFLPs) were first described.[8]

1981: The Venezeula Project was initiated.[9]

1983: The HD gene was mapped to the short arm of chromosome 4.[10]

1989: Linkage disequilibrium indicated a 2 Mb candidate region.[11][12][13]

1993: The HD gene was isolated and a CAG repeat mutation was identified.[14]

1994: The Working Group on HD of the WFN/IHA published guidelines on counseling for predictive testing.[15]

1996: The first mouse model for HD was described.[16]

1997: Aggregates were described in mouse [17] and patient brains.[18]

2000: An inducible mouse model of HD was described.[19]

2001: The first phase-III clinical trials for HD were published.[20]

2002: The first high-throughput screen was published.[21]


Epidemiology

There seem to be an increased prevalence of Huntington's disease among Europeans as compared to Africans and Asians. European populations exhibit a comparatively high prevalence with 4-8 per 100,000 individuals suffering from HD.[22] Two of the most well-known populations in which high prevalence of HD was notably in the state of Zulia, Venezuela[23] and Northern Ireland.[24] The overall prevalence of HD in Mexico was also expected to be comparable or even higher to that of European populations.[25].

Country/Region Prevalence of HD (individuals per 100,000)
Tasmania 12.1 [26]
Northern Ireland 6.4 [27]
South East Wales (UK) 6.2 [28]
Olmsted County, Minnesota (US) 6 - 6.6 (1960) & 1.8 - 2 (1990) [29]
Valencia Region (Spain) 5.38 [30]
Slovenia 5.16 [31]
Oxford Region (UK) 4.0 [32][33]
New South Wales (Australia) 0.65 [34]
Japan 0.65 [35]
Finland 0.5 [36]
Taiwan 0.42 [37]
Hong Kong 0.37 [38]
Table 1 Prevalence of Huntington's Disease in various parts of the world

Table 1 shows the prevalence of HD in different parts of the world, with regions ranked according to how prevalent HD is. Countries with the highest prevalence are from Europe with most appearing at the top of the table whereas Asian countries are found at the bottom half of this table. This indicates the lower prevalence of HD in Asia as compared to that in European populations. This observation is further supported by a study done by Shiwach and Lindenbaum (1990), it was found that the minimum prevalence of HD among immigrants from the Indian subcontinent was found to be almost half that found in the indigenous UK population.[39] For those areas where there are intermarriages with Europeans, there is a higher occurrence of the disease. This is related to the higher frequency of huntingtin alleles with 28–35 CAG repeats in Europeans and the fact the disease is autosomal dominant. [40]


In a paper by Warby et al. (2011), it was reported that HTT haplotypes contribute to the difference in prevalence of HD between European and East Asian populations. Haplotypes are sets of single-nucleotide polymorphisms (SNPs) on a single chromosome of a chromosome pair that are statistically associated. Different HD haplotypes have different mutation rates, resulting in expansion of CAG tract (marker for HD).[41] Hence, for HTT haplotypes with higher mutation risk such as A1 and A2 halotypes, individuals are more susceptible to HD due to CAG expansion and this corresponds to higher prevalence. This is supported by the findings that higher risk A1 and A2 HD halotypes composed the majority of HD chromosomes in Europe whereas it is absent in China and Japan.[42]

HD Halotypes General Population HD Chromosomes
East Asia Europe East Asia Europe
A1 0.00 0.07 0.00 0.50
A2 0.00 0.13 0.00 0.29
B 0.16 0.04 0.10 0.00
C 0.40 0.47 0.77 0.02
Table 2 HTT haplotype frequency in East Asia and Europe [43]


The incidence rate of HD increases with age. It was reported in Taiwan that the range of age at which most onset of HD occurs is between 40-49 years in males and between 50-59 years in females.[44] This trend is similar to that reflected in a Northern Ireland study, whereby the age group in which the highest number of HD onset occurs is 40-44 years.[45] Both of the above-mentioned studies concluded that there is no significant difference for the age of onset between males and females, indicating no sexual predominance for HD.

Treatment

There is no cure for Huntington's disease. Similar to AIDS, only the symptoms of HD can be treated.[46]

Medications

Types of symptoms Types of medications Active chemical ingredient Drugs Possible negative side-effects
Movement disorders Antiseizure drugs

(anticonvulsants)

Valproic acid [47] Depakene Depakote renal toxicity [48][49], hepatoxicity [50], hemorrhagic pancreatitis, coagulopathies, bone marrow suppression and encephalopathy [51]
Lorazepam Ativan sleepiness [52], withdrawal symptoms [53], memory impairment and confusion [54]
Lamotrigine Lamictal chorea [55], toxic epidermal necrolysis [56][57] and multiorgan failure [58]
Levetiracetam [59] Keppra somnolence, lethargy [60], rhinitis, asthenia [61], headache and dizziness [62]
Tetrabenazine [63] Xenazine drowsiness, depression, nausea, worsening of parkinsonism, xerostomia, hypotension [64]
Clonazepam Klonopin Rivotril drowsiness [65], depression, disinhibition and sexual dysfunction [66]
Antianxiety drugs Diazepam Valium Antenex rebound anxiety after withdrawal [67]
Psychiatric disorders Antidepressants Escitalopram Lexapro Lexamil Lexam insomnia, somnolence, dizziness, sweating, constipation, fatigue [68], sexual dysfunction [69], suicidal ideation [70]
Fluoxetine Prozac Sarafem Fontex mania [71], akathisia [72], asthenia, tremor, nausea [73]
Sertraline Zoloft Lustral similar effects to flouxetine and escitalopram: movement disorders and sexual dysfunction [74][75]
Nortriptyline Aventyl Noritren Sensoval Pamelor suicidal ideation [76], hepatic failure [77], dry mouth, sedation, constipation and increased appetite
Mirtazapine Remeron Avanza Zispin dry mouth, sedation, and increases in appetite and body weight [78], restless legs syndrome (RLS) [79]
Antipsychotic drugs Haloperidol Haldol Serenase Linton acute dystonia, akathisia, parkinsonism [80], cognitive decline & brain damage [81]
Clozapine Clozaril Clopine Zaponex agranulocytosis [82], myocarditis [83], gastrointestinal hypomotility [84]
Mood-stabilizing drugs Lithium Lithobid renal failure [85], nystagmus [86], teratogenicity [87]
Carbamazepine Tegretol Carbatol Sirtal congenital malformations [88], pitch perception deficit [89]

Table 3 Symptomatic medications for Huntington's disease

Note: Some drugs have overlapping effects eg. valproic acid and lamotrigine can also used as mood-stabilising drugs.

Disclaimer: The table above is not a comprehensive reference. Please consult your doctor for further information.

Therapies

  • Psychotherapy
  • Speech Therapy
  • Physical Therapy
  • Occupational Therapy

Quite recently, there are a couple of breakthroughs for the treatment of Huntington's.

  • Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. [90]
  • Using adult neurotrophic factor-secreting stem cells. [91]

<a href="http://www.disabled-world.com/health/neurology/breakthrough-cure.php">Huntington's Disease Breakthrough May Provide Cure</a>

References

  1. ↑ Huntington G (1872). "On Chorea". Medical and Surgical Reporter of Philadelphia (The Hague: Nijhoff) 26 (15): 317–321. ISBN 9061860113. [1]
  2. ↑ <pubmed>11232352</pubmed>
  3. ↑ <pubmed>16136077</pubmed>
  4. ↑ <pubmed>11232352</pubmed>
  5. ↑ Hoffmann, J. Über Chorea chronica progressiva (Huntingtonsche Chorea, Chorea hereditaria). Virchows Arch. A 111, 513–548 (1888) (in German)
  6. ↑ On the Origin of Mendelian Genetics Amer. Zool. (1986) 26 (3): 753-768. [2]
  7. ↑ Punnett, R. C. Mendelian inheritance in man. Proc. R. Soc. Med. 1, 135–168 (1908)
  8. ↑ <pubmed>281713</pubmed>
  9. ↑ <pubmed>2881213</pubmed>
  10. ↑ <pubmed>6316146</pubmed>
  11. ↑ <pubmed>2531223</pubmed>
  12. ↑ <pubmed>2531224</pubmed>
  13. ↑ <pubmed>1680285</pubmed>
  14. ↑ <pubmed>8504314</pubmed>
  15. ↑ <pubmed>7966192</pubmed>
  16. ↑ <pubmed>9267033</pubmed>
  17. ↑ <pubmed>8898202</pubmed>
  18. ↑ <pubmed>9302293</pubmed>
  19. ↑ <pubmed>10778856</pubmed>
  20. ↑ <pubmed>11502903</pubmed>
  21. ↑ <pubmed>12200548</pubmed>
  22. ↑ <pubmed>1535611</pubmed>
  23. ↑ <pubmed>2139171</pubmed>
  24. ↑ <pubmed>7562964</pubmed>
  25. ↑ <pubmed>19672992</pubmed>
  26. ↑ <pubmed>2142982</pubmed>
  27. ↑ <pubmed>7562964</pubmed>
  28. ↑ <pubmed>9231935</pubmed>
  29. ↑ <pubmed>8018043</pubmed>
  30. ↑ <pubmed>9528016</pubmed>
  31. ↑ Peterlin B, Kobal J, Teran N, Flisar D, Lovrecić L.Epidemiology of Huntington’s disease in Slovenia. Acta Neurol Scand.: 2009 PMID:18976322 [3]
  32. ↑ <pubmed>21088431</pubmed>
  33. ↑ <pubmed>8108531</pubmed>
  34. ↑ <pubmed>11008591</pubmed>
  35. ↑ <pubmed>8752454</pubmed>
  36. ↑ <pubmed>2889026</pubmed>
  37. ↑ <pubmed>20881427</pubmed>
  38. ↑ <pubmed>7586664</pubmed>
  39. ↑ <pubmed>2151860</pubmed>
  40. ↑ DC Rubinsztein, Molecular biology of Huntington's disease (HD) and HD-like disorders. In: S Pulst, Editor, Genetics of movement disorders, Academic Press, California (2003), pp. 365–377.
  41. ↑ <pubmed>19249009</pubmed>
  42. ↑ <pubmed>21248742</pubmed>
  43. ↑ <pubmed>19249009</pubmed>
  44. ↑ <pubmed>20881427</pubmed>
  45. ↑ <pubmed>7562964</pubmed>
  46. ↑ <pubmed>19588393</pubmed>
  47. ↑ <pubmed>16507108</pubmed>
  48. ↑ <pubmed>8108303</pubmed>
  49. ↑ <pubmed>21868496</pubmed>
  50. ↑ <pubmed>21492891</pubmed>
  51. ↑ <pubmed>18201150</pubmed>
  52. ↑ <pubmed>4341107</pubmed>
  53. ↑ <pubmed>6131080</pubmed>
  54. ↑ <pubmed>3960963</pubmed>
  55. ↑ <pubmed>16900938</pubmed>
  56. ↑ <pubmed>9061826</pubmed>
  57. ↑ <pubmed>12892003</pubmed>
  58. ↑ <pubmed>19380079</pubmed>
  59. ↑ <pubmed>16340384</pubmed>
  60. ↑ <pubmed>18728811</pubmed>
  61. ↑ <pubmed>10908898</pubmed>
  62. ↑ <pubmed>10999557</pubmed>
  63. ↑ <pubmed>16476934</pubmed>
  64. ↑ <pubmed>19050408</pubmed>
  65. ↑ <pubmed>12390050</pubmed>
  66. ↑ <pubmed>2889724</pubmed>
  67. ↑ <pubmed>6145363</pubmed>
  68. ↑ http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-323.pdf_Lexapro_Medr_P1.pdf
  69. ↑ <pubmed>16430968</pubmed>
  70. ↑ <pubmed>19832967</pubmed>
  71. ↑ <pubmed>3485926</pubmed>
  72. ↑ <pubmed>2549018</pubmed>
  73. ↑ http://pi.lilly.com/us/prozac.pdf
  74. ↑ <pubmed>8909330</pubmed>
  75. ↑ <pubmed>11229450</pubmed>
  76. ↑ <pubmed>19832967</pubmed>
  77. ↑ <pubmed>8848811</pubmed>
  78. ↑ <pubmed>11607047</pubmed>
  79. ↑ <pubmed>18756499</pubmed>
  80. ↑ <pubmed>17054159</pubmed>
  81. ↑ <pubmed>18228005</pubmed>
  82. ↑ <pubmed>8515788</pubmed>
  83. ↑ <pubmed>17194170</pubmed>
  84. ↑ <pubmed>18452342</pubmed>
  85. ↑ <pubmed>19940841</pubmed>
  86. ↑ <pubmed>12552061</pubmed>
  87. ↑ <pubmed>11948561</pubmed>
  88. ↑ <pubmed>21127116</pubmed>
  89. ↑ <pubmed>12581810</pubmed>
  90. ↑ <pubmed>19361997</pubmed>
  91. ↑ <pubmed>19603590</pubmed>
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