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Neuropuncture Research
We’re excited to announce the research on Neuropuncture’s Parkinson’s disease prescription began on September 1, 2022.
TITLE of RESEARCH PROJECT:
The Assessment of Neuropuncture™ Electroacupuncture Treatment on Patients with Parkinson’s Disease
OBJECTIVES:
- To demonstrate and document any neurologic improvement of patients with Parkinson’s Disease following Neuropuncture
- To evaluate any post-therapy DaTscan changes from the abnormal pre-therapy DaTscan findings, also utilizing objective data gleaned from our DaT/Quant computer analysis
BRIEF JUSTIFICATION FOR THE PROPOSED RESEARCH PROJECT:
The goal of this investigation is to determine whether Neuropuncture electrical stimulation can regenerate the dopamine secreting neurons of the striata of the basal ganglia. The study will include any measurable impact of the Neuropuncture acupuncture stimulation therapy on (1) patient clinical performance, (2) objective improvement based upon the DaT scan imaging findings, and (3) a saliva neurotransmitter test for dopamine levels.
We propose to perform the Neuropuncture prescription on three patients to determine the efficacy of this Neuropuncture treatment. In addition to documenting improved neurological results, it is important to demonstrate any regeneration of the dopamine neurons in the striata of the basal ganglia that can be revealed using the DaTscan brain SPECT imaging study and objectively document any changes utilizing the DaT/QUANT computer analysis program. The DaTscan results will be compared to normal people of the same age and gender within 2 Standard deviation of the mean.
Furthermore, any increase in the neurotransmitter dopamine may be detected utilizing a specific the salivary neurotransmitter test which will also be performed pre- and post-therapy.
BACKGROUND:
Parkinson’s Disease is one of the most common neurologic disorders and affects about 1% of people over 60 years of age. Nearly one million people will be living with Parkinson’s disease (PD) in the U.S. in 2020, which is more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy, and Lou Gehrig’s disease (Amyotrophic Lateral Sclerosis). Approximately 60,000 Americans are diagnosed with PD each year and approximately 10 million people suffer from PD worldwide. The incidence of Parkinson’s disease increases with age, but an estimated four percent of people with PD are diagnosed before age 50. Men are 1.5 times more likely to have Parkinson’s disease than women. The economic impact is also staggering. Although the progressive disability of this disease can be slowed by medication, it cannot be stopped or reversed. The combined direct and indirect cost of Parkinson’s, including treatment, social security payments and lost income, is estimated to be nearly $52 billion per year in the United States alone. Medications alone cost an average of $2,500 a year and therapeutic surgery can cost up to $100,000 per person. [1]
Deep Brain Stimulation surgery is the most effective therapeutic development since the introduction of levodopa. DBS has recently been approved for patients with early stages of Parkinson’s Disease, that is, patients that have had the disease for at least 4 years and are poorly controlled with medication. It is especially useful in treating patients with severe tremors and medication side effects, including dyskinesias. These salutary effects may last at least five years. Thus, DBS is not a cure-all and may not slow PD progression. It may also not improve speech impairment, cognition, swallowing difficulties or gait disturbances. [1]
In a small number of patients, DBS brain surgery may result in infection, bleeding, CVA, and seizures. Some PD patients also suffered a decline in cognition post DBS surgery. [1]
We propose a non-invasive treatment of PD with little or no serious side-effects. Studies have shown that electrical acupuncture can benefit Parkinson’s patients without surgery or medication. [6,7] Research further has presented potential neuroscience mechanisms for the positive effects. [9,10,12] Some studies report increases in neurotransmitter production [13], while others provide images of the brain that are being activated by the electrical acupuncture stimulation. [11] Dopamine is the main neurotransmitter that is dysfunctional, and the striata of the basal ganglia are the cerebral regions of focus. Neuropuncture is a neuroscience acupuncture system that utilizes electrical stimulation of the acupuncture needles placed into the scalp and body to transmit a specific electrical current dosage to that targeted pathological neural tissue in an attempt to neuromodulate, neuro-regulate, and/or neuro-rehabilitate the nervous system (basal ganglia) back into homeostasis. [2-3]
Anecdotally, we have two case studies supplied from Neuropuncture practitioners. Dr Satish Nair, ND, and Dr. Helen Law, PhD, treated patients with the Neuropuncture Parkinson’s Disease therapeutic regimen similar to our Neuropuncture prescription, and documented on video and reports that major objective improvement in the patient’s performance following treatment were observed [4].
METHOD:
The Neuropuncture Parkinson’s treatment prescription is a non-invasive electrical acupuncture treatment. The Neuropuncture Parkinson’s treatment prescription consists of two components. The first is to target the release of tyrosine hydroxylase in the brain. The second component is to target the basal ganglia specifically as well as produce BDNF (brain derivative neurotropic factor), GDNF (glia derivative neurotropic factor), SOD (superoxide dismutase), and dopamine. All the electrical acupuncture techniques were created by implementing the Neuropuncture acupuncture system’s theory and clinical strategies by one of the investigators (M.C.). Specific Neuropuncture points of the scalp adjacent to certain nerves have already been identified that can influence the neuroplasticity of the brain. [5]
This prescription will be standardized for each patient but may be altered in the future upon full agreement of all the investigators prior to instituting the research project. This will ensure that each treated patient will undergo the exact same Treatment Prescription. The Neuropuncture treatments will be performed by specially trained licensed acupuncturists.
The proposed electrical dosage will be 4-100 Hz of millicurrent applied to each needle. The Electrical acupuncture stimulator that will be used is the Pantheon 8C and delivers a bi-phasic square waveform. This is a FDA registered medical device specifically for electrical acupuncture. [14]
The DaT scan with Brain SPECT and DaT/QUANT computer analysis will be performed prior to the Neuropuncture therapy. The routine technique will be utilized. One-hour following administration of a thyroid blocking agent, 5 mCi of I-123 Ioflupane will be injected intravenously. The brain SPECT study will be performed three hours later. The acquisition time is approximately 30 minutes. Data will be reconstructed using iterative reconstruction and displayed in the axial plane for interpretation. Quantitative computer processing using the DaT/QUANT computer analysis program will also be performed and will provide Z scores and % deviation from the mean scores of persons of the same age and gender without neurodegenerative disease.
We will perform pre- and post-treatment DaT scans. The pre-therapy DaT scan will be performed within 60 days prior to the neurostimulation treatment and serve as the baseline study. The post therapy DaT scan will be performed within one month after treatment. The DaT scans will be interpreted by a trained board-certified nuclear medicine physician.
A saliva neurotransmitter taste will also be taken pre- and post-neurostimulation therapy to measure the dopamine levels. (ZRT Lab).
The Neuropuncture electrical acupuncture treatment will be performed two times per week for six weeks, totaling twelve Neuropuncture treatment sessions. The patient will then be reevaluated by a neurologist for any change in clinical performance. This neurologic clinical reassessment will determine if further neurostimulation treatment is indicated. The post-therapy DaT scan will be performed within 30 days post therapy.
LOCATION:
St. Joseph University Medical Center (Hospital) in Paterson, NJ will be the primary institution where the research will be performed. We expect most of the patients will be St. Joseph’s outpatients referred by hospital staff neurologists. The study is also opened to non-St. Joseph Hospital outpatients and patients referred by non-staff neurologists, however. Preferably, the DaT/scans will be performed at St. Joseph University Medical Center. With some exceptions when travel to St. Joseph University Medical Center is not feasible, the DaT scan may be performed at another institution and the study electronically sent to St. Joseph’s Nuclear Medicine Department for review using the same parameters.
PATIENT SELECTION:
Patient inclusion criteria: male and female 50-75 years of age. Only patients with referred by neurologist suspected of having PD and present with an abnormal DaTscans will be entered into the study. All patients will be required to sign a consent form. Exclusion criteria: Obviously, pregnant women and those under the age of under 50 years old and older then 75 will be excluded from the study. No patients that have underwent DBS will be included. Patients may be recruited by hospital staff neurologists, non-hospital-staff neurologists, and by GE Public Relations personnel. Recruitment by way of social media may be also considered, but PD patients must first be evaluated by a qualified board-certified neurologist and demonstrate a positive DaT brain SPECT scan.
Clinical assessment of defined neurologic parameters with scoring will be performed prior to and after treatment. This assessment will be standardized for each patient. Some include cognitive impairment, fine motor skill impairment, bradykinesia, ataxia, tremors, cog-wheel rigidity, lack of fine motor skills, emotional changes, hallucinations, etc. We will be using the UPDRS [8], as follows:
UNIFIED PARKINSON’S DISEASE RATING SCALE (UPDRS)
I. MENTATION, BEHAVIOR AND MOOD
1. Intellectual Impairment
0 = None
1 = Mild. Consistent forgetfulness with partial recollection of events and no other difficulties.
2 = Moderate memory loss, with disorientation and moderate difficulty handling complex problems. Mild but definite impairment of function at home with need of occasional prompting.
3 = Severe memory loss with disorientation for time and often to place. Severe impairment in handling problems.
4 = Severe memory loss with orientation preserved to person only. Unable to make judgements or solve problems. Requires much help with personal care. Cannot be left alone at all.
2. Thought Disorder (Due to dementia or drug intoxication)
0 = None
1 = Vivid dreaming.
2 = “Benign” hallucinations with insight retained.
3 = Occasional to frequent hallucinations or delusions; without insight; could interfere with daily activities.
4 = Persistent hallucinations, delusions, or florrid psychosis. Not able to care for self.
3. Depression
0 = None.
1 = Periods of sadness or guilt greater than normal, never sustained for days or weeks.
2 = Sustained depression (1 week or more).
3 = Sustained depression with vegetative symptoms (insomnia, anorexia, weight loss, loss of interest).
4 = Sustained depression with vegetative symptoms and suicidal thoughts or intent.
4. Motivation/Initiative
0 = Normal.
1 = Less assertive than usual; more passive.
2 = Loss of initiative or disinterest in elective (nonroutine) activities.
3 = Loss of initiative or disinterest in day to day (routine) activities.
4 = Withdrawn, complete loss of motivation.
II. ACTIVITIES OF DAILY LIVING (for both “on” and “off”)
5. Speech
0 = Normal.
1 = Mildly affected. No difficulty being understood.
2 = Moderately affected. Sometimes asked to repeat statements.
3 = Severely affected. Frequently asked to repeat statements.
4 = Unintelligible most of the time.
6. Salivation
0 = Normal.
1 = Slight but definite excess of saliva in mouth; may have nighttime drooling.
2 = Moderately excessive saliva; may have minimal drooling.
3 = Marked excess of saliva with some drooling.
4 = Marked drooling, requires constant tissue or handkerchief.
7. Swallowing
0 = Normal.
1 = Rare choking.
2 = Occasional choking.
3 = Requires soft food.
4 = Requires NG tube or gastrotomy feeding.
8. Handwriting
0 = Normal.
1 = Slightly slow or small.
2 = Moderately slow or small; all words are legible.
3 = Severely affected; not all words are legible.
4 = The majority of words are not legible.
9. Cutting food and handling utensils
0 = Normal.
1 = Somewhat slow and clumsy, but no help needed.
2 = Can cut most foods, although clumsy and slow; some help needed.
3 = Food must be cut by someone but can still feed slowly.
4 = Needs to be fed.
10. Dressing
0 = Normal.
1 = Somewhat slow, but no help needed.
2 = Occasional assistance with buttoning, getting arms in sleeves.
3 = Considerable help required, but can do some things alone.
4 = Helpless.
11. Hygiene
0 = Normal.
1 = Somewhat slow, but no help needed.
2 = Needs help to shower or bathe; or very slow in hygienic care.
3 = Requires assistance for washing, brushing teeth, combing hair, going to bathroom.
4 = Foley catheter or other mechanical aids.
12. Turning in bed and adjusting bed clothes
0 = Normal.
1 = Somewhat slow and clumsy, but no help needed.
2 = Can turn alone or adjust sheets, but with great difficulty.
3 = Can initiate, but not turn or adjust sheets alone.
4 = Helpless.
13. Falling (unrelated to freezing)
0 = None.
1 = Rare falling.
2 = Occasionally falls, less than once per day.
3 = Falls an average of once daily.
4 = Falls more than once daily.
14. Freezing when walking
0 = None.
1 = Rare freezing when walking; may have start Hesitation.
2 = Occasional freezing when walking.
3 = Frequent freezing. Occasionally falls from freezing.
4 = Frequent falls from freezing.
15. Walking
0 = Normal.
1 = Mild difficulty. May not swing arms or may tend to drag leg.
2 = Moderate difficulty but requires little or no assistance.
3 = Severe disturbance of walking, requiring assistance.
4 = Cannot walk at all, even with assistance.
16. Tremor (Symptomatic complaint of tremor in any part of body)
0 = None.
1 = Slight and infrequently present.
2 = Moderate; bothersome to patient.
3 = Severe; interferes with many activities.
4 = Marked; interferes with most activities.
17. Sensory complaints related to parkinsonism
0 = None.
1 = Occasionally has numbness, tingling, or mild aching.
2 = Frequently has numbness, tingling, or aching; not distressing.
3 = Frequent painful sensations.
4 = Excruciating pain.
III. MOTOR EXAMINATION
18. Speech
0 = Normal.
1 = Slight loss of expression, diction and/or volume.
2 = Monotone, slurred but understandable; moderately impaired.
3 = Marked impairment, difficult to understand.
4 = Unintelligible.
19. Facial Expression
0 = Normal.
1 = Minimal hypomimia, could be normal “Poker Face”.
2 = Slight but definitely abnormal diminution of facial expression.
3 = Moderate hypomimia; lips parted some of the time.
4 = Masked or fixed facies with severe or complete loss of facial expression, lips parted 1/4 inch or more.
20. Tremor at rest (Head, upper and lower extremities)
0 = None.
1 = Slight and infrequently present.
2 = Mild in amplitude and persistent. Or moderate in amplitude, but only intermittently present.
3 = Moderate in amplitude and present most of the time.
4 = Marked in amplitude and present most of the time.
21. Action or Postural Tremor of hands
0 = Normal.
1 = Slight; present with action.
2 = Moderate in amplitude, present with action.
3 = Moderate in amplitude with posture holding as well as action.
4 = Marked in amplitude; interferes with feeding.
22. Rigidity (Judged on passive movement of major joints with patient relaxed in sitting position. Cogwheeling to be)
0 = Absent.
1 = Slight or detectable only when activated by mirror or other movements.
2 = Mild to moderate.
3 = Marked, but full range of motion easily achieved.
4 = Severe, range of motion achieved with difficulty.
23. Finger Taps (Patient taps thumb with index finger in rapid succession.)
0 = Normal.
1 = Mild slowing and/or reduction in amplitude.
2 = Moderately impaired. Definite and early fatiguing. May have occasional arrests in movement.
3 = Severely impaired. Frequent hesitation in initiating movements or arrests in ongoing movement.
4 = Can barely perform the task.
24. Hand Movements (Patient opens and closes hands in rapid succession.)
0 = Normal.
1 = Mild slowing and/or reduction in amplitude.
2 = Moderately impaired. Definite and early fatiguing. May have occasional arrests in movement.
3 = Severely impaired. Frequent hesitation in initiating movements or arrests in ongoing movement.
4 = Can barely perform the task.
25. Rapid Alternating Movements of Hands (Pronation-supination movements of hands, vertically and horizontally, with as large an amplitude as possible, both hands )
0 = Normal.
1 = Mild slowing and/or reduction in amplitude.
2 = Moderately impaired. Definite and early fatiguing. May have occasional arrests in movement.
3 = Severely impaired. Frequent hesitation in initiating movements or arrests in ongoing movement.
4 = Can barely perform the task.
26. Leg Agility (Patient taps heel on the ground in rapid succession picking up entire Amplitude should be at least 3 inches.)
0 = Normal.
1 = Mild slowing and/or reduction in amplitude.
2 = Moderately impaired. Definite and early fatiguing. May have occasional arrests in movement.
3 = Severely impaired. Frequent hesitation in initiating movements or arrests in ongoing movement.
4 = Can barely perform the task.
27. Arising from Chair (Patient attempts to rise from a straight-backed chair, with arms folded across )
0 = Normal.
1 = Slow; or may need more than one attempt.
2 = Pushes self-up from arms of seat.
3 = Tends to fall back and may have to try more than one time but can get up without help.
4 = Unable to arise without help.
28. Posture
0 = Normal erect.
1 = Not quite erect, slightly stooped posture; could be normal for older person.
2 = Moderately stooped posture, definitely abnormal; can be slightly leaning to one side.
3 = Severely stooped posture with kyphosis; can be moderately leaning to one side.
4 = Marked flexion with extreme abnormality of posture.
29. Gait
0 = Normal.
1 = Walks slowly, may shuffle with short steps, but no festination (hastening steps) or propulsion.
2 = Walks with difficulty, but requires little or no assistance; may have some festination, short steps, or propulsion.
3 = Severe disturbance of gait, requiring assistance.
4 = Cannot walk at all, even with assistance.
30. Postural Stability (Response to sudden, strong posterior displacement produced by pull on shoulders while patient erect with eyes open and feet slightly Patient is prepared.)
0 = Normal.
1 = Retropulsion but recovers unaided.
2 = Absence of postural response; would fall if not caught by examiner.
3 = Very unstable, tends to lose balance spontaneously.
4 = Unable to stand without assistance.
31. Body Bradykinesia and Hypokinesia (Combining slowness, hesitancy, decreased arm swing, small amplitude, and poverty of movement in)
0 = None.
1 = Minimal slowness, giving movement a deliberate character; could be normal for some persons. Possibly reduced amplitude.
2 = Mild degree of slowness and poverty of movement which is definitely abnormal. Alternatively, some reduced amplitude.
3 = Moderate slowness, small amplitude of movement.
4 = Marked slowness, small amplitude of movement.
CONTROL GROUP:
These patients will be treated by their neurologist with medication only. Depending upon the ongoing results, these patients may be eligible to crossover to the Neuropuncture group if there is no improvement on medication and approval of the referring neurologist.
FUNDING:
The G. Dolph Corradino Neuropuncture Research Non-profit Corporation will be the major source of funding. We are attempting to request funding from Parkinson’s Disease non-profit organizations, Parkinson Study Group, and other private avenues. Expense includes pre- and post DaTscans and salvia neurotransmitter tests.
Estimated costs:
- DaT-Scans: $2500.00 per scan, (each patient will need a post-therapy study).
- Salvia tests: $149.00 per test, (each patient will need pre- and post-therapy).
- Maximum estimated cost per patient = $6,000.00
REFERENCES:
- Parkinson’s disease foundation: https://parkinson.org
- Jaung-Geng Lin, et al. “Electroacupuncture promotes recovery of motor function and reduces dopaminergic neuron degeneration in rodent models of Parkinson’s disease.” International Journal of Molecular Sciences, August 2017, https://www.mdpi.com/1422-0067/18/9/1846
- Xiang Shen, et al. “Effects of electroacupuncture on cognitive function in rats with Parkinson’s disease.” International Journal of physiology, pathophysiology, and pharmacology, 2015, pp 145-151. https://ncbi.nlm.nih.gov/pmc/articles/PMC4697670/
- “Anectodical” Dr Satish Nair, ND treated patient with the Neuropuncture PD Rx for PD and documented major objective improvement in patient
- Eberhard Fuchs and Gabriele Flugge. “Adult neuroplasticity: more than 40 years of ” Hindawi-neural plasticity. 2014. https://doi.org/10.1155/2014/541870
- Ji-Sheng Han, et al. “Electroacupuncture: mechanisms and clinical application.” Society of biological 1998, pp 129-138.
- Xu W, OuYang S, Chi Z, Wang Z, Zhu D, Chen R, Zhong G, Zhang F, Zhou G, Duan S, Jiao| Effectiveness and safety of electroacupuncture in treating Parkinson disease: A protocol for systematic review and meta-analyses. Medicine (Baltimore). 2021 Mar 12;100(10):e25095. doi: 10.1097/MD.0000000000025095.PMID: 33725902 https://pubmed.ncbi.nlm.nih.gov/33725902/
- The Unified Parkinson’s Disease Rating Scale (UPDRS): Status and Recommendations Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease Movement Disorders 18, No. 7, 2003, pp. 738–750 2003 Movement Disorder Society
- Kathy Sato: THE BENEFITS OF NEURO-ACUPUNCTURE, Dec 7, 2019 | Dec 2019 – Jan 2020, Health, |Generations Magazine
- Starkey Jamie: Acupuncture’s Increasing Credibility in Research and Clinical Settings – Alternative and Complementary February 2018, 24(1): 7-9. Published in Volume: 24 Issue 1: February 1, 2018
- Nam MH1, Ahn KS, Choi SH: Acupuncture Stimulation Induces Neurogenesis In Adult Brain. Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
- Sujung Yeo, MD, PhD, Maurits van den Noort, PhD, Peggy Bosch, PhD, and Sabina Lim, MD, PhD: A study of the effects of 8-week acupuncture treatment on patients with Parkinson’s Medicine (Baltimore). 2018 Dec; 97(50): e13434 Published online 2018 Dec 14.
- Yeo S, Lim S, Choe IH, Choi YG, Chung KC, Jahng GH, Kim SH: Acupuncture stimulation on GB34 activates neural responses associated with Parkinson’s disease. CNS Neuroscience 2012 Sep;18(9):781-90
- Pantheon Research
PRINCIPAL INVESTIGATORS:
- Michael D. Corradino, MSTOM, DAOM, AP.
Neuropuncture Inc.
Boynton Beach, FL 33436
E-mail: neuropuncture@gmail.com - Patrick J. Conte, MD, PhD
Chief, Nuclear Medicine Senior Attending, Department of Radiology St. Joseph University Medical Center
Paterson, New Jersey
E-mail: drpjconte@aol.com - Thomas Gormley, DMD, FAGD, NCCAOM, LAc, MSAc
Senior Attending, Department of Dentistry, Chief of Integrative Medicine Department of Family Medicine
St. Joseph University Medical Center
Paterson, New Jersey
Email: gormleyth@sjhmc.org
APENDIX A:
NEUROPUNCTURE TREATMENT OF PATIENTS WITH PARKINSON’S DISEASE
Name_____________________________________________Date of Birth________________
Medical Record No._________________________________Telephone __________________
Male ____Female________Age __ Date _______________________________ __
Chief Complaint:______________________________________________________________
Symptoms and when first began:_________________________________________________
Findings: _____________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
Patient’s Signature_____________________________________________________________
MEDICAL ACUPUNCTURE CLINIC QUESTIONS
Name ____________ __________Date of Birth ________________Date____________________
What is your chief complaint?
Consent obtained.
Do you have any pain? Describe:
Do you feel hot or cold?
How is your sleep?
What is your energy level?
How is your breathing?
Do you have any heart or circulation problems?
Do you have any stomach or digestive concerns?
Do you have any problems with urination?
Do you have any bowel movement problems?
Do you have menstrual problems / erectile dysfunction problems?
How is your mood?
Concerns with medication?
Any other concerns?
__________________________________________________________________________________
For Doctor
Tongue: _____________________________________________________________________
Pulse:_ _______________________________________________________________________
TCM Dx: ______________________________________________________________________
Acupuncture needles placed ______________________________________________________
Points: _______________________________________________________________________
Post Op Rx: _Recommendation – ____________________________________________________
APENDIX B:
Note about GABA and Enkephalin with electrical dosage and the role of neuropeptides with their neurologic pathways: Parkinson’s Disease is a neurodegenerative movement disorder in which the dopamine circuit and neurochemistry become deficient resulting in impaired physical performance, blunted emotional responses, and diminished cognitive abilities. The main medical focus of pathology and treatment in PD has been at the basal ganglia level, specifically the dopaminergic system. There are two dopamine pathways that become neurodegenerative, the direct and indirect pathways. The direct pathway is the nerve circuitry responsible for causing bradykinesia, slow movements, and rigidity. The indirect dopamine pathway is responsible for the resting tremors. Both dopamine pathways target specific dopamine receptors, D1 and D2. The direct pathway is activated by dopamine and has a GABA component. The indirect pathway has an enkephalin component. The unique Neuropuncture PD electrical acupuncture treatment prescription includes components to target dopamine, GABA, and enkephalin release as well as their manufacture. This information is supported with published medical research. This unique combined acupuncture point selection along with the specific electrical dosages chosen activates this neuromodulating effect and, hopefully, objective neuroregeneration. We will be assessing any evidence of neuroregeneration with the post-therapy DaT/scan findings.
NORMAL Dat/scan and DaT/Quant analysis
ABNORMAL DaT/scan and DaT/Quant analysis
The posterior putamen is the first structure showing decreased tracer uptake in Parkinson’s Disease
