A Case of MS & Chronic Migraines: Treatment Using LDN & the Wahls Protocol

2021 Student Scholarship – First Place Case Study

HEIDI CODINO 

ANGELA HARDIN, ND

Multiple sclerosis (MS) is the most common demyelinating, chronic, inflammatory disease of the central nervous system (CNS).¹ MS courses of disease are either relapsing-remitting (RRMS) or primary and secondary progressive.^1,2 Approximately 90% of patients with MS have the RRMS type when first diagnosed, while the remaining approximate 10% are diagnosed with the primary progressive form, which has the worst prognosis.¹ All forms of MS present with several symptoms and comorbidities, which are widely variable among patients.^2,3 These symptoms may include but are not limited to: numbness, insomnia, weakness, Lhermitte’s sign (electric shock sensation in the neck), disturbances in gait, coordination and vision, tremors, fatigue, neuropathy, depression, and migraine headaches.³ Standard-of-care treatments for MS include the use of monoclonal antibodies that target the CD20 antigen on B-cells, thereby reducing the attack of B-cells on oligodendrocytes and significantly slowing disease progression.¹ Treatment for MS relapses commonly includes intravenous corticosteroids, physical therapy, and narcotics.¹ 

Migraine pain, which is located either unilaterally or bilaterally in the temporal or occipital regions, may or may not be preceded by aura and is typically characterized as throbbing. Aura, which is defined as transient neurological symptoms, occurs prior to the onset of migraine pain and lasts 5-60 minutes in duration.^4,5 Migraines are most commonly accompanied by symptoms of nausea, vomiting, photophobia, phonophobia, anorexia, and vertigo.^4,5 Migraines are commonly triggered by dehydration, food sensitivities, bright lights, loud noises, strong aromas, certain medications, alcohol, or high stress, and are influenced by some genetic variants.^4,6 Migraine headaches are considered chronic when such symptoms are present for 15 days or more each month, for at least 3 consecutive months.⁴ Standard-of-care treatments for migraine headaches include removal of recognizable triggers to help prevent their occurrence, and first-line abortive treatments, such as over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) or triptan medications.^4,5  

The following case study investigated the efficacy of low-dose naltrexone in reducing the frequency and severity of chronic migraine headaches in a patient with MS. 

Case Study 

Presenting Concerns & Clinical Findings 

A 62-year-old female with previously diagnosed RRMS initially presented to clinic seeking adjunctive treatment for her chronic, debilitating, intractable migraines without aura. She had received the MS diagnosis in 2007. She reported migraine episodes that lasted from 30 to 90 days in duration, equating to approximately 50-70% of the month and 60% of the year. Her migraine pain would typically begin as sharp, “like rusty nails,” and right-sided, and would then progress to the eyes, jaw, and parietal regions, where it felt “like a vice.” The severity of her symptoms ranged from 6/10 to 10/10 (10 being the worst). She reported concomitant symptoms of nausea, vomiting, anorexia, blurred vision, photophobia, and phonophobia during these episodes. Her headache triggers included increased stress, dehydration, and consumption of red wine or chocolate cake. The patient also suffered from many MS-related symptoms, including depression, insomnia, neuropathy, and impairments in gait, coordination, and cognition.  

The patient was diagnosed with osteoporosis by dual energy X-ray absorptiometry (DEXA) scan after a fall in June of 2020. Her past medical history was also significant for herpes zoster and insomnia. Her family history of neurological conditions was unknown.  

The patient’s current medications included bisphosphonates (70 mg weekly), venlaxafine (250 mg daily), and vitamin D3 (2000 IU daily). For migraine relief, she had previously tried multiple botulinum injections, valproic acid (250 mg), ketolorac injections, galcanezumab, and supplementation with butterbur and magnesium, all of which brought little to no symptom benefit.

Table 1. Patient Timeline  

Date	Visit Summary	Intervention
2/1/20	Initial visit: CC: Migraine headaches, with episodes lasting 2-3 months in duration; intractable to multiple treatments Relevant past medical history: MS diagnosis in 2007. Migraines began after this.	LDN:1.5 mg/d for 1 week; increase by 1.5 mg weekly, to max dose of 4.5 mg/d   Wahls Protocol® recommended
3/21/20	Follow-up: Reports significant reduction in migraine headache frequency, duration, and intensity	Continue LDN at 4.5 mg/d   Continue Wahls Protocol®
8/17/20	Follow-up: Reports continued reduction in migraine headache frequency, duration, and intensity (only 1-2 migraine headaches/month since last visit) Reports improved sleep quality, energy, mobility, and cognition Reports temporary discontinuation of LDN for 7 weeks	Due to lapse in LDN use, a titrated dose schedule was reinitiated:  LDN: 1.5 mg/d for 1 week; increase by 1.5 mg weekly, to max dose of 4.5 mg/d   Continue Wahls Protocol®
12/7/20	Phone call: Reports continued reduction in migraine headache frequency, duration, and intensity (only 1 migraine episode since last visit) Reports significant increase in quality of life since treatment initiation	Continue LDN at 4.5 mg/d   Continue Wahls Protocol®

Diagnostic Assessment 

The diagnosis of MS is largely dependent on medical history and the presence of neurological deficits.⁷ Such deficits must be localized, present for at least 24 hours, and not due to infection.⁷ There are no laboratory tests specific to MS; however, a complete blood count (CBC), complete metabolic panel (CMP), thyroid panel, lipid panel, viral serology, and antinuclear antibodies (ANA) are typically investigated to exclude other causes of neurological deficits.⁷ A diagnosis of MS can be confirmed with magnetic resonance imaging (MRI), demonstrating dissemination in time and space in localized areas of the central nervous system.⁷ A lumbar puncture to analyze the cerebrospinal fluid can also confirm a diagnosis.⁷  

The prognosis of MS is dependent on age of onset, the treatments utilized, and the degree of disease progression.⁸ Untreated patients have a 30% chance of developing physical disabilities that will significantly impact their lives within 20-25 years following symptom onset.⁸ MS has a slight impact on shortening life expectancy, with patients typically dying from secondary complications.⁸  

Migraines are diagnosed clinically, based upon the patient’s reported symptoms, as well as symptom severity, duration, and quality.⁴ The duration of migraine headaches is typically between 4 and 72 hours; however, episodes may last up to several months at a time. There are currently no lab tests or imaging that can definitively diagnose migraines, but MRI or computed tomography (CT) scans are often used to rule out more concerning acute pathologies, such as stroke, space-occupying lesions, and temporal arteritis.⁴  

The prognosis of chronic migraine headaches in MS is very good if the patient receives appropriate treatment to control the symptoms and prevent future migraines.⁹ Medication overuse and lack of treatment adherence are indicators for a poor prognosis.⁹  

This patient presented to clinic with an existing RRMS diagnosis and was being managed by a neurologist. Her migraines had been recurrent for more than 3 consecutive months, with episodes lasting longer than 72 hours and occurring more frequently than 15 days per month. They were, by definition, chronic. 

Therapeutic Intervention 

Naltrexone is an opioid antagonist that is typically used to treat drug and alcohol addiction, at oral doses of 25 50 mg, or 380 mg intramuscularly.¹⁰ Low-dose naltrexone (LDN), at doses of 5 mg and lower, are used in the treatment of several chronic pain syndromes and autoimmune conditions.¹¹ LDN has been demonstrated to reduce pain and depression, improve physical function, and increase quality of life in patients with chronic pain.¹¹ It acts as an antagonist on toll-like receptor 4 (TLR-4) and it modulates glial cells, which downregulate cytokines, thereby reducing inflammation and associated pain.¹²  

A titration schedule of LDN should be utilized to minimize possible disturbances in sleep (eg, vivid dreams and/or insomnia) and gastrointestinal side effects (eg, nausea, cramping, vomiting, and/or diarrhea). The patient was instructed to follow the titration schedule of 1.5 mg nightly for the first week, 3 mg nightly for the second week, then 4.5 mg nightly thereafter.  

The Wahls Protocol® is a dietary regimen created by Terry Wahls in 2008 based on her research of the many health effects of modifiable lifestyle measures.¹³ This protocol has been studied extensively in patients with MS and other autoimmune conditions. This diet emphasizes the consumption of a minimum of 9 cups of fruits and vegetables per day; with the addition of 1 serving each of seaweed, algae, and nutritional yeast; 12 ounces of lean, organic, grass-fed organ meats per week; and 16 ounces of fish per week. In addition, the elimination of gluten, grains, legumes, eggs, dairy, and nightshade vegetables is recommended¹³ due to the potential for these foods to contribute to inflammation in persons with autoimmune disorders, thus worsening symptoms. The Wahls diet is rich in flavonoids and other antioxidants, which have been demonstrated to reduce inflammation by downregulating cytokines and reducing the formation of free radicals.¹³ 

The patient was educated on the details of the Wahls Protocol and encouraged to begin the diet immediately. 

Patient Follow-ups  

One Month Later 

At the patient’s 1-month follow-up visit, she reported decreases in the frequency, severity, and duration of her migraine headaches, as well as improved sleep. She was encouraged to maintain the Wahls diet as long as she continued to note symptom improvement. 

Eleven Months Later 

During the 11 months since her last follow-up visit, the patient remained compliant with LDN and the Wahls Protocol, with the exception of a 7-week lapse in LDN use due to a temporary change in evening routine. During that period, she had instances of migraine headaches with increased intensity and duration; this also occurred when she deviated from the dietary protocol. 

She reported that, in general, her quality of life had significantly improved, and her migraine headaches had reduced to a total of 3 episodes, each one lasting 2-3 days since initiating treatment. She also reported reductions in pain severity, improvements in fatigue, sleep, and mood, and increased physical mobility. Her only reported side effect was vivid dreams, which did not disturb her sleep or cause her to discontinue the protocol. She reported noticing benefit from the combination treatments beginning approximately 6 weeks following initiation. 

The patient was ecstatic that after many years of suffering from severely debilitating, long-lasting migraine headaches without previous relief, she found the recommended protocols to be “life changing.” She also reported that her neurologist was “very happy” with the results of these treatments and encouraged her to continue them.  

Discussion 

The strengths of this case were the patient’s significant symptom improvement and adherence to the recommended treatment protocols. A limitation of the case was the simultaneous initiation of LDN and the Wahls Protocol. This made it difficult to identify the specific source of her significant symptom improvement, which could be due to the reduction in inflammation from LDN or the removal of inflammatory foods, the increase in antioxidant-rich foods, or the combination of these factors. Another limitation was that the Wahls Protocol can be difficult to maintain for long periods of time due to its restrictive nature and its demands related to supply sourcing and preparation. Future considerations should include a trial involving a less restrictive diet.  

Although the patient reported that she did not suffer from migraine headaches until after her MS diagnosis in 2007, it is difficult to know whether the patient’s migraines were a symptom of MS or a separately occurring disorder. The marked reduction in her migraine symptoms with the aforementioned protocols warrants further investigation in patients with similar symptoms. The use of 1 or both of these treatment protocols should be considered in the future in patients with MS and/or chronic migraine headaches. 

References: 

1. Macaron G, Ontaneda D. Diagnosis and Management of Progressive Multiple Sclerosis. Biomedicines. 2019;7(3):56.  

2. Trapp BD, Bö L, Mörk S, Chang A. Pathogenesis of tissue injury in MS lesions. J Neuroimmunol. 1999;98(1):49-56.  

3. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502-1517.  

4. Weatherall MW. The diagnosis and treatment of chronic migraine. Ther Adv Chronic Dis. 2015;6(3):115-123. 

5. Rohmann JL, Rist PM, Buring JE, Kurth T. Migraine, headache, and mortality in women: a cohort study. J Headache Pain. 2020;21(1):27. 

6. Gormley P, Winsvold BS, Nyholt DR, et al. Migraine genetics: from genome-wide association studies to translational insights. Genome Med. 2016;8(1):86.  

7. Ömerhoca S, Akkaş SY, İçen NK. Multiple Sclerosis: Diagnosis and Differential Diagnosis. Noro Psikiyatr Ars. 2018;55(Suppl 1):S1-S9.  

8. Luzzio C. Multiple Sclerosis. Prognosis. Updated September 2, 2020. Medscape. Available at: https://emedicine.medscape.com/article/1146199-overview#a6. Accessed September 15, 2020.  

9. Probyn K, Bowers H, Caldwell F, et al. Prognostic factors for chronic headache: A systematic review. Neurology. 2017;89(3):291-301.  

10. MedlinePlus. Naltrexone. Last revised October 15, 2017. Available at: https://medlineplus.gov/druginfo/meds/a685041.html. Accessed September 16, 2020.  

11. Noon K, Sturgeon J, Kao M, et al. (Abstract 418): A novel glial cell inhibitor, low dose naltrexone, reduces pain and depression, and improves function in chronic pain: A CHOIR study. J Pain. 2016;17(4 Suppl):S79.  

12. Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 2018;6(4):82.   

13. Wahls TL, Chenard CA, Snetselaar LG. Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic. Nutrients. 2019;11(2):352.  

Heidi Codino is a 4th-year medical student at the National University of Natural Medicine (NUNM). Prior to medical school, Heidi received her BSc in Psychology, with an emphasis in Research, from Washington State University. Heidi will be applying for residency in the 2021 cycle and will graduate in June of 2021 from NUNM with a Doctorate in Naturopathic Medicine as well as a Natural Childbirth Certificate. Heidi wishes to heal using all modalities that are warranted, while starting with the foundations of health. She is very passionate about underserved populations, making sure that they have equity in healthcare. 

Angela Hardin, ND is a licensed naturopathic physician completing her second year of residency at NUNM. Dr. Hardin offers medical care for individuals seeking integrative primary care, as well as offering support for mental health, gastrointestinal, reproductive and neurologic disorders, and chronic pain. She has been a licensed massage therapist for many years and has completed additional trainings in craniosacral and pelvic floor rehabilitation therapies. Dr. Hardin’s mission in medicine is to create and uphold a safe, unbiased healing space for all patients. She is especially passionate about serving transgender individuals and military veterans.