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Disclaimer: The material presented in this site is intended for public educational purposes only. The author is not offering medical or legal advice. Accuracy of information is attempted but not guaranteed. Before undertaking any diet, or health improvement program, you should consult your physician. The author is in no way liable or responsible for any bodily harm, physical, mental or emotional state of any patient reacting to any of the content on this site. Thetinman.org has not examined, reviewed or tested any product or service mentioned herein. We are not being paid to advertise or promote any product or service mentioned herein. The links are offered strictly as examples of resources available. The site assumes no responsibility or liability of any kind related to the content of external sites or the usage of any product or service referenced. Links to external sites were live at the time of creation of the link. Thetinman.org does not create content for or manage external sites. The information can be changed or removed by the external site’s administrators at any time and they are responsible for the veracity of their information. Links are provided to support our data and supply additional resources. Please report broken links to administrator@thetinman.org. Thetinman.org is not a charitable foundation. It neither accepts nor distributes donations or funds of any kind.
1. Botulinum Toxin A injections, Botox, Dysport, Xeomin, MyoBloc
Botulinum toxin is a protein and neurotoxin produced by the bacterium Clostridium botulinum. It is the most acutely lethal toxin known, with an estimated human median lethal dose (LD-50) of 1.3–2.1 ng/kg intravenously or intramuscularly and 10–13 ng/kg when inhaled. Botulinum toxin (BTX) can cause botulism, a serious and life-threatening illness in humans and animals. Three forms of botulinum toxin type A (Botox, Dysport and Xeomin) and one form of botulinum toxin type B (MyoBloc) are available commercially for various cosmetic and medical procedures. The toxin works only on each muscle injected, so it may not be the best option for multiple muscles. The injections must be repeated at frequent intervals. The body can create antibodies against the medication which can neutralize the effects. Drugs.com.
1. Botulinum Toxin Use Link to article
2. Anagnostou E, Zambelis T. Botulinum toxin A in anti-GAD-positive stiff-limb syndrome. Muscle Nerve. 2012 Sep;46(3):457-8. doi: 10.1002/mus.23416. Link to article
3. Davis D, Jabbari B. Significant improvement of stiff-person syndrome after paraspinal injection of botulinum toxin A. Mov Disord. 1993 Jul;8(3):371-3. Link to article
Diazepam and Lioresal offered partial pain relief. Paraspinal muscle administration of botulinum toxin A reduced the tone of paraspinal and thigh muscles significantly and resulted in marked improvement of ambulation and cessation of pain.
4. Liguori R, Cordivari C, Lugaresi E, et al. Botulinum toxin A improves muscle spasms and rigidity in stiffperson syndrome. Mov Disord 1997, 12:1060–1063. Link to article
BTA administration significantly reduced rigidity and stopped the spasms in all limbs. Following BTA injection on one side, the spasm frequency decreased bilaterally possibly because of the spread of hematogenous toxin.
5. Monnier G, Tatu L, Michel F. New indications for botulinum toxin in rheumatology. Joint Bone Spine. 2006 Dec;73(6):667-71. Epub 2006 Aug 30. Review. Link to article
Preliminary data have been obtained in patients with cervical or thoracolumbar myofascial pain syndrome, chronic low back pain, piriformis muscle syndrome, tennis elbow, and stiff person syndrome. At present, the effects of botulinum toxin and its use for pain relief. remain controversial.
2. Cannabinoids, Sativex, Nabilone, Cesamet, Dronabinol, Epidiolex
The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands, and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs.
The most psychoactive cannabinoid found in the cannabis plant is tetrahydrocannabinol (or delta-9-tetrahydrocannabinol, commonly known as THC). Other cannabinoids include delta-8-tetrahydrocannabinol, cannabidiol (CBD), cannabinol (CBN), cannabicyclol (CBL), cannabichromene (CBC) and cannabigerol (CBG); they have less psychotropic effects than THC, but may play a role in the overall effect of cannabis. The most studied are THC, CBD and CBN. CBD is considered to have a wider scope of medical applications than tetrahydrocannabinol (THC). An orally-administered liquid containing CBD has received orphan drug status in the US, for use as a treatment for dravet syndrome. Drugs.com.
1. Vicente-Valor MI, Garcia-Llopis P, Mejia Andujar L, et al. Cannabis derivatives therapy for a seronegative stiff-person syndrome: a case report. J Clin Pharm Ther. 2013 Feb;38(1):71-3. doi: 10.1111/j.1365-2710.2012.01365.x. Epub 2012 Jun 21. Link to article
“Clinical experience with cannabis derivatives in patients with multiple sclerosis is accumulating steadily, but there is no current literature about its efficacy for SPS. Because MS and SPS share some neurological symptoms such as spasticity and rigidity, it is thought that THC-CBC can be an option for SPS patient. Our case report suggests that THC-CBD oromucosal spray is an alternative treatment for patients with refractory SPS, and further validation is appropriate.”
2. Medical marijuana Extract Cannabidiol (CBD) Shows Therapeutic Benefit For Multiple Sclerosis (MS). Drugs.Com
3. Clomipramine (SSRI), Anafranil
Clomipramine is a tricyclic antidepressant (TCA). Clomipramine withdrawal can be severe. Clomipramine is a highly selective (200x over norepinephrine) inhibitor of serotonin reuptake. It is also an antagonist/inverse agonist at the histamine H1 receptor, the muscarinic acetylcholine receptors and the α1 adrenergic receptor. These last three actions likely contribute to its adverse effects. Drugs.com.
1. Meinck HM, Ricker K, Conrad B. The stiff-man syndrome: new pathophysiological aspects from abnormal exteroceptive reflexes and the response to clomipramine, clonidine, and tizanidine. J Neurol Neurosurg Psychiatry 1984, 47:280–287.
“Clomipramine injection severely aggravated the clinical symptoms whereas diazepam, clonidine, and tizanidine decreased both muscular stiffness and abnormal exteroceptive reflexes. The hypothesis is put forward that the stiff-man syndrome is a disorder of descending brain-stem systems which exert a net inhibitory control on axial and limb girdle muscle tone as well as on exteroceptive reflex transmission.”
4. Clonidine, Catapres, Kapvay, Nexiclon, Clophelin
Clonidine is a sympatholytic medication used to treat high blood pressure, attention-deficit/hyperactivity disorder, anxiety disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. It is classified as a centrally acting α2 adrenergic agonist and imidazoline receptor agonist. Drugs.com.
1. Meinck HM, Ricker K, Conrad B. The stiff-man syndrome: new pathophysiological aspects from abnormal exteroceptive reflexes and the response to clomipramine, clonidine, and tizanidine. J Neurol Neurosurg Psychiatry 1984, 47:280–287. Link to article
“Clomipramine injection severely aggravated the clinical symptoms whereas diazepam, clonidine, and tizanidine decreased both muscular stiffness and abnormal exteroceptive reflexes. The hypothesis is put forward that the stiff-man syndrome is a disorder of descending brain-stem systems which exert a net inhibitory control on axial and limb girdle muscle tone as well as on exteroceptive reflex transmission.”
5. Interferon
Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as viruses, bacteria, parasites, or tumor cells. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to ramp up their anti-viral defenses. IFNs belong to the large class of glycoproteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infection. IFNs also have other functions: they activate immune cells, such as natural killer cells and macrophages; they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (MHC) antigens.
Interferon beta-1a and interferon beta-1b are used to treat and control multiple sclerosis. This treatment is effective for reducing attacks in relapsing-remitting multiple sclerosis and slowing disease progression and activity in secondary progressive multiple sclerosis. Interferon therapy is used (in combination with chemotherapy and radiation) as a treatment for some cancers. Drugs.com
1. Scavone G, Zaccardi F, Manto A, Caputo S, Pitocco D, Ghirlanda G. A case of chronic hepatitis C developing insulin-dependent diabetes, thyroid autoimmunity and stiff-person syndrome as complications of interferon therapy. Diabetes Res Clin Pract. 2010 Aug;89(2):e36-8. doi: 10.1016/j.diabres.2010.05.006. Epub 2010 Jun 11. Link to article
We describe the case of a 66-year-old man with chronic hepatitis C who developed type 1 diabetes mellitus (T1DM) and thyroid autoimmunity during Interferon α (INFα) therapy and then stiff-person syndrome (SPS). This is the first reported case in which SPS has appeared as complication of IFNα therapy.
6. L-Dopa, Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa.
L-3,4-dihydroxyphenylalanine) is a chemical that is made and used as part of the normal biology of humans, some animals and plants. Some animals and humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines. L-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; As a drug it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia. Drugs.com.
1. Guilleminault J, Sigwald J, Castaigne E. Sleep studies and therapeutic trial with L-Dopa in a case of stiff-man syndrome. Eur Neurol 1973;10:89-96. Link to article
“ A case of Stiffman syndrome was followed for several years. A trial with L-dopa was performed after diazepam withdrawal. All-night polygraphic monitorings of the patient’s sleep under diazepam, under no drugs, and under L-dopa were performed. An analysis of sleep stages and electromyographic changes was obtained. A new benzodiazepine (Ro 054023) was tried after L-dopa.”
7. Milacemide
Milacemide is a MAO-B inhibitor and glycine prodrug. It has been studied for its effects on human memory and as a potential treatment for the symptoms of Alzheimer's disease. Early clinical trials, however, showed no positive results. The drug research now is abandoned.
1. Brown P, Thompson PD, Rothwell JC, et al. A therapeutic trial of milacemide in myoclonus and the stiffperson syndrome. Mov Disord 1991, 6:73–75 Link to article
“We investigated the therapeutic effects of milacemide in seven patients with myoclonus and three patients with the stiff-person syndrome in an open-label trial. Milacemide was initiated at 800 mg/day and was gradually increased to a maximum dosage of 2,400 mg/day. No significant improvement occurred in the 10 patients.”
2. Gordon MF, Diaz-Olivo R, Hunt AL, Fahn S. Therapeutic trial of milacemide in patients with myoclonus and other intractable movement disorders.Movement Disorders. 1993;8:4, 484-488
We performed a therapeutic trial with the glycine precursor, milacemide, on 10 patients with intractable movement disorders. Six had myoclonus of various etiologies and one each had progressive supranuclear palsy, Filipino X-linked dystonia with parkinsonism, painful legs and moving toes, and stiff-person syndrome. Milacemide was initiated at a dose of 2,400 mg/day, orally, and increased gradually to a maximum of 4,800 mg/day. No clear-cut observable improvement occurred. There were no serious adverse effects.
EXPERIMENTAL TREATMENTS
Treatment options GABAergic drugs GABA A Agonists GABA Modulators GABA B Agonists GABA P Agonists
GABA Transaminase GABA RUI GABA Analogues GABA Supplement Muscle Relaxers Corticosteroids
Antiseizure Opiate Analgesics Experimental IVIG Plasmapheresis Immunotherapy Stem Cell Therapy PT
Disclaimer: The material presented in this site is intended for public educational purposes only. The author is not offering medical or legal advice. Accuracy of information is attempted but not guaranteed. Before undertaking any diet, or health improvement program, you should consult your physician. The author is in no way liable or responsible for any bodily harm, physical, mental or emotional state of any patient reacting to any of the content this site. Thetinman.org has not examined, reviewed or tested any product or service mentioned herein. We are not being paid to advertise or promote any product or service mentioned herein. The links are offered strictly as examples of resources available. The site assumes no responsibility or liability of any kind related to the content of external sites or the usage of any product or service referenced. Links to external sites were live at the time of creation of the link. Thetinman.org does not create content for or manage external sites. The information can be changed or removed by the external site’s administrators at any time and they are responsible for the veracity of their information. Links are provided to support our data and supply additional resources. Please report broken links to administrator@thetinman.org.