Day-to-Day Management of Mitochondrial Disease

Cristy Balcells, RN, MSN MaryBeth Hollinger, RN, MSN

MitoAction’s vision is to create a community of support that reaches every child, adult, and caregiver affected by a mitochondrial disease.

While helping families living today with mitochondrial disease, we strive

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• To improve quality of life for adults and children affected by mitochondrial disease.

• To raise awareness internationally about mitochondrial disorders and their relationships to other diseases.

• To provide specific and practical materials that help patients to manage their symptoms.

• To aggregate and connect the international mitochondrial disease community and to engage the pharmaceutical industry working toward therapeutic approaches to mitochondrial disorders.

• To create tools that empower patients and caregivers to be advocates for themselves or their children.

Mitochondrial Disease

• Simply stated: Mito is an energy shortage within the body!

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• Mitochondria, tiny organelles within the cell -- the powerhouse of the cell -- create 90% of cellular energy.

• Mitochondrial failure causes cell injury that leads to cell death. When multiple cells die within an organ, symptoms of organ failure arise.

www.bbc.com

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Does this look like Mito?

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Symptoms are variable!

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• Multi-system symptoms typically involve three or more body systems which may appear unrelated or without identifiable cause.

• Body functions and organ systems that are high demand are impacted most significantly: brain and nerves, GI, eyes, ears, liver, heart, pancreas, kidneys, and muscles.

Red Flag Symptoms

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• Non-vascular stroke-like lesions, neurodegeneration, ataxia, MRI findings consistent with Leigh's diseaseHypertrophic cardiomyopathy, unexplained heart block in a child, cardiomyopathy with lactic acidosisRetinal degeneration with night blindness, ptosisSevere GI dysmotility, unexplained or valproate-induced liver failureRhabdomyolysis, FTT, hypersensitive to general anesthesia, exercise intolerance not in proportion to weakness

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Described in detail on Mitochondrial Medicine Society website (www.mitosoc.org)

Associated Symptoms

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• Hypotonia, intractable epilepsy, hearing loss

• Tachycardia, including postural

• Optic nerve hypoplasia, pigmentary retinopathy

• CVS, chronic, unexplained constipation or diarrhea

• Hypothyroidism, hypoparathyroidism

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Renal tubular dysfunction, aminoaciduria, nephrotic syndrome

• Basal ganglia lesions, CNS atrophy

• History of SIDS, multigenerational maternal inheritance patterned migraines, depression, or anxiety

• Go to www.mitosoc.org for a full list

Diagnostic Process• Mito is difficult to diagnosis for many and may

take many years, especially for the adult patient.

• Ruling OUT other more common diseases takes time.

• Negative tests have a high false-negative rate,which adds to confusion!

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Keep in Mind

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•The classification system for mitochondrial disease is incomplete and not clinically oriented.

•The abnormality can vary from tissue to tissue within the same person, and perhaps within the same organ as well.

•There is no consistent diagnostic abnormality for all patients with mitochondrial disease (Haas, 2007).

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Metabolic screening of blood and urine

• Metabolic screening of CSF if neurological symptoms

• Evaluating systemic or organ involvement

• Genetic studies if above points to Mito

Testing typically includes:

Mito Specialists

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• More are needed across the USA and beyond

• Difficult to get initial appointment because of demand

• Primary care is needed to forge a path to diagnosis

• MitoAction -- http://www.mitoaction.org/doctors

• MMS Interactive map -- http://www.mitosoc.org/clinics/

Referral Process

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• Establish a working relationship with medical team: primary, neurologist, ophthalmologist, and/or any area where symptoms are of concern and not explained by other causes.

• Primary care doctors can order many of the initial tests required to begin the diagnostic process.

• Medical evidence consistent with a mitochondrial issue strengthens a referral to a specialist.

First Appointment!

• Tool Kit http://www.mitoaction.org/mito-navigator-toolkit-overview

• Communication

• Medical Records

• Support

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Social Media Guidelines

PCP Interaction

Medical Home

Medical Professionals

Record keeping for Improved

Communication

Sharing Research Findings

Becoming a Great Advocate

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Ge t More f rom Eve r y Appointment

Communication Resourceswww.mitoaction.org

Records

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• Obtain copies of medical records -- part or whole

• PCP as keeper of full records -- Medical Home

• Emergency Protocol letters

Support

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• Support groups

• Family and Friends

• Counseling and Hotline Support

Symptom Management

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• The treatment of Mito includes treating each body system with dysfunction, even with Mito as the underlying cause.

• Many Mito patients, therefore, see multiple specialists, making effective communication vital.

• Nutrition, hydration, energy management and the Mito cocktail are the cornerstones to management.

Dysautonomia

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Disorder of the Autonomic Nervous System

• POTSTemperature dysregulationCardiac, GI, nervous, respiratory system and more

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POTS

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Can severely impact life!

Types -- Partial, Hyperadrenergic, & Secondary

Highly recommend watching Dr. Blair Grubbs’ podcasts and reading his publications.

Under supervision of a physician:

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• Reconditioning program -- 20-30 minutes of aerobic exercise three times per week

• Resistance training of lower extremities

“LOW AND SLOW!”

Use PT or cardiopulmonary rehab for support

Exercise!

Grubb, B., Journal of Cardiovascular Electrophysiology, 2006

Under supervision of a physician:

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• Fluids -- 2-3 L+ a day. Gatorade and milk preferred.

• Salt (3,000-10,000 mg daily) in pill form, salty snacks, or added to food

• Compression stockings (30-40 mmHg pressure, waist high)

• Raise HOB

• Avoid substances and situations that worsen symptoms (dehydration, extreme heat, prolonged sitting and standing, alcohol, caffeine)

http://www.dysautonomiainternational.org/

Medications

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Fludrocortisone

Beta Blockers

Midodrine

Clonidine

Pyridostigmine

Benzodiazepines

SSRIs

SNRIs

Erythropoietin

Octreotide

http://www.dysautonomiainternational.org/

Heat IntoleranceMay be associated with inability to sweat, elevated body temperature, red or mottled skin, dramatic loss of stamina and/or muscle tone.

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Hydrate -- begin before going out! Cooling vestsLight, breathable layers of clothing Baggies with wet wash clothsAvoid being outside at hottest times of the day Plan ahead -- shade, fans, water to cool off

Cold Intolerance

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Exposure to cold temperature can cause muscle pain and fatigue as the muscles work harder to generate heat.

• Layers of clothing, especially wool

Be aware of malls, hotels, conference, offices, and restaurants with A/C

Hand and foot warmers, seat warmers, electric blanket and mattress pads

Warm car before heading out

Consume hot foods and drinks

Plan ahead with extra clothing (damp/wet clothes)

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ProtocolsMitoAction has printable protocols and strategies developed by Dr. Mark Korsen and Maggie Orr, RN, including:

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• Fever and Infection

• Vomiting

• School

• Anesthesia, procedures and surgery

http://www.mitoaction.org/protocol

Nausea, Vomiting, Diarrhea, Constipation, GI Pain, Anorexia

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Mitochondrial function and energy production are dependent upon good nutrition and hydration. Fasting can cause critical energy shortages in a child or adult with Mito. A team approach is vital to maintain hydration and nutrition.

• Small, frequent meals of easy to digest food/drinks

• GT or JT feeding when needed: TPN when oral feeds fail to maintain weight

• Overnight feeds may be especially beneficial

• Zorfran and Benadryl for nausea

• Stool softeners, laxatives and extra fluids for constipation

• Abdominal pain may be treated by combination of medications such as amitriptyline and prokinetics to improve motility

Vomiting and Diarrhea

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Gut may not be able to tolerate much for 12-24 hours after virus and may takes weeks or months to fully recover. Use IV support if needed.

• Begin small! 1 tsp of clear liquid every 30 minutes and progress slowly if tolerated.

• BRAT diet when tolerated

• Balance high-calorie foods with digestible foods

• Treat underlying causes aggressively. Germ avoidance!

Protocol: http://www.mitoaction.org/files/protocol-vomiting.pdf

FeverFever dramatically increases the body’s energy demand, which can be associated with lethargy, regression, weakness, and metabolic crises.

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Fever should be treated aggressively with fluids and medications (ibuprofen and acetaminophen).

Have a plan in place of when to call Primary, what actions to take, and when to go to ER.

Protocol: http://www.mitoaction.org/files/protocol- fever-and-infection.pdf

Pain, Fatigue, Weakness

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• Pain -- one of the greatest challenges as pain consumes physical and emotional energy

• Chronic pain is difficult to treat effectively

• Pain often leads to depression, anxiety, and feelings of hopelessness, especially when ignored by family and medical team

• Migraines, abdominal, muscle, & nerve pain are common

• When pain is controlled, other symptoms are easier to manage

Migraines

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• Avoid triggers -- Sleep, timing of meals, infection, exhaustion, dehydration, hormone fluctuations.

• Keep headache, food, sleep, and general trigger logs to find potential triggers!

• Have a plan for acute pain relief.

• Hydration, nutrition, rest, and exercise are key!

Nerve Pain

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Neuropathy -- ranges from tingling to deep, burning, aching pain, or stabbing shocks. Numbness can occur.

• May be helped by Mito supplements, namely ALA, CoQ10, and Carnitine

• PT, hydration, and Neurotin (gabapentin) are frequently prescribed

Muscle Pain

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Deep aching pain, especially in arms, legs and back that tends to be worse when lactic acid levels are high.

• Pain management should be a priority. Keep a pain/trigger log.

• Medications, including Marinol, may be needed to stay ahead of the pain.

• PT, OT, exercise, yoga

• Accupressure, chiropractic measures, relaxation techniques

• Palliative care, focus on quality of life, and pain centers offer big picture approaches to pain.

Myopathy

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• Includes weakness, low stamina, “floppy,” low tone, pain, exercise intolerance

• Adhere to plans for hydration and nutrition

• Carnitine, creatine, and CoQ10

• Build rest periods into day -- respect limits

• Exercise -- Builds better mitochondria

Seizures & Stroke-Like Events

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Literature suggests that over 60% of Mito patients have seizures or will develop seizures. Many children have difficult to manage seizures.

• Again -- log to uncover triggers -- hypoglycemia, fatigue, stress, hydration

• Ketogenic Diet under direct medical care

• Meds often vital -- although avoid valproic acid

Stoke-like episodes (SLE) – cardinal feature in lactic acidosis, encephalomyopathy, and MELAS. SLE is not a true vascular stroke, but considered to be a metabolic stroke.

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• Can look like vascular strokes with aphasia, hemiparesis, and facial weakness.

• Acute in onset, often transient/reversible, and occasionally associated with a febrile illness.

• Vastly different medical histories than typical stroke patients.

(JAMA Neurology, 2016).

“Although much information is still needed regarding the appropriate dosage and timing of arginine therapy in patients with MELAS, urgent administration of nitric oxide precursors in patients with MELAS ameliorates the clinical symptoms of stoke-like episodes.”

www.ncbi.nlm.nih.gov/pubmed/26954033(JAMA Neurology, 2016)

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MitoAction summary of MMS full update: http://www.mitoaction.org/blog/mitochondrial-medicine-society- update-2016

MMS Consensus Protocol - SLE

MMS Protocol

IV Arginine - - 0.5 gm/kg/day for 3-5 days while patient has symptoms

Maintenance -- PO Arginine 0.3 gm/kg/day

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Depression & Anxiety

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• The human brain uses 23% of a body’s daily energy -- the biggest energy demand of all!

• Mito causes disregulation of the cells’ ability to make energy, causing symptoms throughout the body.

• Dysregulation in the brain causes depression, anxiety and other issues.

• Approximately 80% of patients with Mito experience anxiety and/or depression.

• Coping with chronic illness is also tied to depression.

Reality for Many

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• Psych symptoms are overlooked due to medical crises, therefore little help or support is offered.

• Body and mind are not viewed as interactive parts of whole body.

• Psych symptoms are viewed as hypochondria, overreacting, somatoform, or Munchausen Syndrome.

• Bottom line -- patients suffer and QOL is impacted.

• Cognitive Behavior Therapy

• Medications -- and doses may not be typical (think outside the box!)

• Mito cocktail -- especially B vitamins, creatine and CoQ10

• Exercise, yoga, stress management

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Puberty•

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Metabolic stress of puberty onset Added energy demands of growth Changes in hormonesChange in sleep patterns

For some teens, add:•

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Social changes School pressures More lossesUnique differences compared with peers Increased awareness of their future

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www.zits.com

Puberty Brings• Increase in severity of symptoms/new symptoms

• Increase in autonomic system symptoms

• Menstruation

• Depression, anxiety, irritability, mood swings

• Non-compliance with treatment

• Desire for independence

www.zits.com

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Hints

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• Puberty is hard on the parent, too -- find support.

• Teens need MORE support during this time -- emotionally and physically.

• Shortened school day, fewer classes, home instruction, extended year, online classes

• Technology aids to save energy (voice to type)

• Support for school stress and life stress

• Extra set of books, IEP, 504 plans

• Hobbies are vital!

• Be available to listen, guide, and adapt current plans.

• Throw away time frames -- Let school and life happen at its own pace.

• Be mindful of the pros and cons of social media.

Doggie Bag*(*take-home points)

• Plan ahead for everything to save time and energy in the long run!

• Consistency matters -- rest, fluids, nutrition, exercise, meds.

• Avoid all triggers, including germs.

• Remember to breathe and LIVE life (focus on the important things that bring joy to your day and take a break from Mito!).

• Protocols can help take the pressure off the family.

• Seek support -- setback are likely and the losses are real.

• Continue to raise Mito awareness -- become an advocate!

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Thank you to all for listening today, for your ongoing support, and for sharing your stories with our Mito community.

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Additional Reading

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www.MitoAction.org

Balcells, Cristy. Living Well with Mitochondrial Disease, 2012.

Mitochondrial Medicine Society - www.mitosoc.org

MMS Stroke protocol- http://www.ncbi.nlm.nih.gov/ pubmed/26954033