dementia

Animal study demonstrating CBD’s (cannabidiol) effects on neuroplasticity and memory loss

Virginia Thornley, M.D.
Neurologist, Epileptologist
August 26, 2019
In an animal study, one group demonstrates that Cannabidiol may help with the neuroplasticity in patients with Alzheimer’s disease (1).
LTP in the hippocampus is the long-term potentiation seen that elevates the efficacy of synapses involved in memory. Beta-amyloid peptide is toxic towards this  feature. When animals were pretreated with CBD the neurotoxicity was found to be reduced against beta-amyloid peptide. The same study showed that it did not involve the 5-HT1a, CB1 or adenosine receptors (1).
There have been other previous studies showing that cannabidiol could have protective effects against the toxic effects of beta-amyloid peptide which is involved in the neurodegenerative process seen in Alzheimer’s disease.
More clinical randomized control trials are needed. Animal studies do not always translate into human studies.
Neurologybuzz.com
References
  1. Hughes, B., Herron, C.E., Cannabidiol reverses deficits in hippocampal LTP in a model of Alzheimer’s disease. Neurochem. Res. 2019, Mar. 44(3):703-713

This is medical information not medical advice. Please consult with your physician.

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cannabidiol

How does cannabidiol (CBD) help with skin disorders

Virginia Thornley, M.D.
Neurologist, Epileptologist
April 3, 2019
Introduction
Cannabidiol has been in the news lately blown up by the media as the miracle cure. You see anecdotal information that it works for various conditions. The research has been slow since it was previously a  schedule 1 agent and is now declassified. Attention is now turned to the different conditions where it might work including dermatologic disorders. But what are the mechanisms?
 
Mechanisms how cannabidiol might work in dermatologic disorders.
Melanogenesis occurs as  protection from dangerous factors such as UV radiation exposure. In one study,  cannabidiol increases MITP or microphthalmia associated transcription factor through one pathway involved in MAPK (mitogen activating protein kinase) phosphorylation of p38 as well as p42 MAPK.
Potential effects on acne vulgaris
Cannabidiol was found to reduce the multiplication of sebocytes, the cells in the sebaceous glands by activating the TPRV channels (transient receptor potential of vanilloid). It reduces the production of the oily substances from the skin. It controls inflammation by inhibition of the NF-kB signalling
Potential effects on psoriasis
Cannabinoids are found to reduce proliferation of cancer cells in cell lines in some studies. One study sought to study reduction of keratinocytes in an inflammatory condition such as psoriasis. It was found it can reduce the proliferation but may not contribute significantly to the process.
References
  1. Kim, M.O., Kang, M., Oh, S.W., Nho, Y.H., Park, S.H., Lee, J., Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact 2017, Aug;273:107-114
  2. Olah, A., Toth, B., Borbiro, I, Sugawara, K., Szoliosi, A.G., Czifra, G., Pal, B., Ambrus, L., Kloepper, J., Camera, E., Ludovici, M., Picardo, M., Voets, T., Zouboulis, C.C., Paus, R., Biro, T. Cannabidiol exerts sebostatic and anti-inflammatory effects on human sebocytes, J. Clin Invest. 2014 Sep; 124(9):3713-24
  3. Wilkinson, J.D., Williamson, E.M. Cannabinoids inhibit keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J. Dermatol. Sci 2007 Feb; 45(2):87-92
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cerebral atrophy

Can anti-psychotic agents reduce brain volume?

Virginia Thornley, M.D.
Neurologist, Epileptologist
July 10, 2019
Can medications cause cerebral atrophy. Cerebral atrophy refers to shrinkage of the cells causing the appearance of the brain to have less volume than usual.
This question was asked last week. An anti-epileptics such as phenytoin is well-known in the literature and clinically to cause cerebellar atrophy. But what about other agents such as anti-psychotics?
Animal studies
In one animal study, exposure to anti-psychotic drugs showed a reduced volume of brain on volumetric studies. The number of cells remained the same but the volume was increased for cells in the anterior cingulate gyrus which is in the  limbic lobe. The limbic lobe subserves emotions and has influence on memory. Animal studies do not always correlate with human responses.
Human studies
One small study showed that the thalamic volume was reduced after olanzepine administration. This was a small study of 10 patients (2).
While there is some information in the literature, the studies are animal studies and a small human study. More information is needed. Based on the current literature, there are not enough significant studies to correlate atrophy with use of anti-psychotics.
Neurologybuzz.com
References
  1. Vernon, A.C., Crum, W.R., Lerch, J.P., Chege, W., Natesan, S., Modo, M., Cooper, J.D., Williams, S.C., Kapur, S. Reduced cortical volume and elevated astrocyte density in rats chronically treated with anti-psychotic drugs-linking magentic resonance imaging findings to cellular pathology. Biol Psychiatry. 2014, Jun. 15, 75(12):982-90
  2. Khorram, B., Lang, D.J., Kopala, L.C., Vandorpe, RF.A., Rui, Q., Goghari, V.M., Smith, G.N., Honer, W.G. Reduced thalamic volume in patients with chronic schizophrenia after switching from typical anti-psychotic medications to olanzepine. Am J sychiatry. 2006, Nov. 163 (11):2005-7
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dementia

Can anti-cholinergics cause dementia?

Can anti-cholinergics cause dementia?
Virginia Thornley, M.D., Neurologist, Epileptologist
July 1, 2019
In one study, they found that anti-cholinergic agents shows an increased risk of dementia. In the study, certain anti-depressants and urologic agents were found to correlate more with the risk of dementia including dosulepine, duloxetine and amitriptyline for the anti-depressants and tolteridine and oxybutinin for the urologic agents (1).
There are thoughts that there is a risk of dementia even 2 decades after the exposure. Certain anti-Parkinson’s agents were found to possible correlate with dementia. Anti-cholinergic agents have consistently been associated with problems with short-term memory.
Neurologybuzz.com
Reference
1.Richardson, K., Fox, C., Maidment, I, Steel, N., Loke, Y, Arthur, A., Myint, P., Grossi, C., Mattishent, K., Bennett, K., Campbell, N., Boustani, M., Robinson, L., Brayne, C., Matthews, F., Savva, G. Anti-cholinergic drugs and risk of dementia: case-control study, BMJ, 2018; 361
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multiple sclerosis, Uncategorized

The impact of immunomodulating agents used in multiple sclerosis on the risk of cancer

Virginia Thornley, M.D., Neurologist, Epileptologist
June 14, 2019
Introduction
Multiple sclerosis is already an illness where the immune system recognizes the nervous system specifically the white matter tracts as foreign and attacks it. The complex cascade of mechanisms make adequate treatment challenging. Many treatments focus on the inflammatory mechanism with little attention on the degenerative mechanism involved.
Presentation of symptoms come in a wide variety depending on the the location of the multiple sclerosis plaque in the brain.
Patients may have concomitant morbidities which may make treatment challenging.
 
Immunomodulating agents and its impact on cancer
Many of the newer treatments for multiple sclerosis work at the level of the immune system through immunosuppression, the newer ones tend to be very potent. With greater efficacy comes greater risks including the risk of cancer.
Some of the newer medications can potentially increase the risk of cancer. Higher risk of cancer was found in many reports to occur with use of cyclophosphamide, azathioprine and mitoxanthrone. Fingolimod, natalizumab and alemtuzamab  can potentially increase the risk of cancer, these agents lack long-term data and work through the immune system. Dimethyl fumarate, terifluonimide, ocrelizumab, daclizumab and cladribine merit mandatory risk management plans to detect cancer before its use.
Reference
  1. Lebrun, C., Rocher, F., Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs. CNS Drugs. 2018, Oct. 32(10):939-949 doi:10.1007/s40263-018-0564-y
Disclaimer: This is medical information only not medical advice. Please consult your physician
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cerebellar ataxia

Genetics of Hereditary Cerebellar Ataxia and Hereditary Spastic Paraplegia

Virginia Thornley, M.D.
Neurologist, Epileptologist
March 18, 2019
Introduction
Cerebellar ataxias are rare disorders, only a few types are treatable. This reviews some of the research regarding the genetics of cerebellar ataxias.
Next generation sequencing is a revolutionary way of DNA sequencing that can sequence an entire genome in one day which previously took 10 years. Clinical applications are still pending (1).
Genetics of hereditary cerebellar ataxias
In one study of 87 patients, the genetics were studies. In the probands meaning the first in a genetic line, triplet repeat testing was done. 58% were male. Genetic variants included ANO10, CACNA1A, SPG7 and DRKCG. The detection rate in probands for the trinucleotide repeat was about 13.8%. Those with variants may have a longer duration of disease and a slower progression of the disorder (2).
 
Genetic testing in hereditary spastic paraparesis
In another study where 306 were genetically tested, next generation sequence testing was performed and different genes were found. These include ATL1 (atlastin 1, SPG3),
PAST (spastin, SPG4),  ITPR1, WASHC5 (SPG8),  KIF1A (SPG30), SPG11 spastacsin), KIF5A (SPG10), CYP27A1, and SETX (3).
There are overlapping genetics and clinical symptoms with spinocerebellar ataxia and amyotrophic lateral sclerosis.
Reference
  1. Behjati, S., Tarpey, P., What is next generation sequencing? Arch Dis Child Educ Pract Ed. 2013 Dec; 98(6)236-238
  2. Kang, C., Liang, C., Ahmad, K.E., Gu, Y., Siow, S.F., Colebatch, J.G., Whyte, S., N, K., Cremer, P.D., Corbett, A.J., Davis, R.L., Roscioloi, T., Cowley, M.J., Park, S.J., Sue, C.M., Kumar, K.R. High Degree of Genetic Hetereogeneity for Hereditary Cerebellar Ataxias in Australia, Cerebellum, 2019, Feb. (1):137-146
  3. Elert-Dobkowska, E., Stepniak, I., Krysa, W., Ziora-Jakutowicz, K., Rakowicz, M., Sobanska, A., Pilch, J., Antczak-Marach, D., Zaremba, J., Sulek, A. Next-generation sequencing reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes. Neurogenetic, 2019, Feb, doi:10.1007/s10048-019-00565-6
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fibromyalgia

Review of scientific literature: can diet alleviate symptoms from fibromyalgia

Virginia Thornley, M.D., Neurologist, Epileptologist
October 15, 2018
Introduction
There is growing interest in lifestyle changes in controlling certain diseases especially those that are related to inflammation. This seeks to review the scientific literature and determine if there is any science supporting any evidence for recommend dietary changes to alleviate symptoms from fibromyalgia.
Possible mechanisms underlying fibromyalgia
Fructose is a molecule that is not absorbed well in the gut and is related to low levels of tryptophan causing tryptophan to be absorbed less in the gut. Tryptophan is the precursor of serotonin or 5-HT which is found to be low in patients with fibromyalgia (1). Fructose is widely seen in the western diet present in honey and sweeteners known as high fructose corn syrup.
Fructose malabsorption in the gut may contribute towards increased fructose and interefere with tryptophan absorption (1).
Low fructose diet
In one case report a diet was devised where fructose was excluded so as to allow increased tryptophan availablility. The diet consisted of eggs, fish, clams, meat, celery, spinach, beets, dark chocolate, walnuts, carrots, potatoes, chard, grape seed oil, thyme, sage, carob powder, millet, green tea, small amount of almonds, coffee and rosemary. Sodas and processed food were deleted from the list. Legumes, cereal, wheat and fructan-containing vegetables and inulin containing vegetables were excluded. The diet is comprised of 25-27% proteins, 9-10% fiber, 31-36% carbohydrates and 30-32% fats. The patient’s previous diet consisted of the Mediterranean diet which has 50% carbohydrates (2). While fructose may be excluded in a diet, this may reduce the caloric intake which would be detrimental. Any diet that is developed should  not neglect the caloric intake.
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After 12 months, the patient was found to have less pain and could do aerobic exercises due to her pain-free state. There were some times she did not strictly adhere to the diet which resulted in a flare-up of the pain. It is also indicative that a modified diet is not curative short-term. This indicates that the results from the diet are not related to a placebo effect. More studies are needed. This study supports the growing interest of low levels of tryptophan, which is a precursor of 5-HT, as contributing towards the mechanisms causing pain in fibromyalgia (2).
 
Other factors that contribute towards fibromyalgia
Women seem to be more prone to symptoms of fibromyalgia. While the level of 5-HT is similar in men and women, women seem to synthesize 5-HT at a reduced rate compared to men (1).
Stress and anxiety leads to increase of glucocorticoids which may also interfere with 5-HT synthesis (1).
 
In summary
There is increasing biochemical information that fructose may contribute towards the pathophysiology involved in fibromyalgia. Growing interest is directed towards the use of certain diets to control the symptoms of fibromyalgia, however, large clinical human trials are needed.
While there is scientific biochemical information, large human trials are needed. There is not enough information to recommend this until large human clinical trials are performed.
References
1. Lattanzio, S.M. Fibromyalgia syndrome: a metabolic approach grounded in the biochemistry for the remission of symptoms Front. Med. 2017, Nov. 4:198
2. Lattanzio, S.M., Imbesi, F. Fibromyalgia syndrome: a case report on controlled remission of symptoms by a dietary strategy. Front med. 2018, 5:94
This is for informational purposes only and does not constitute medical advice, see your physician. Large human randomized controlled clinical trials are needed.
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