Parkinson Disease

Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites.

Signs and symptoms

Initial clinical symptoms of Parkinson disease include the following:

• Tremor
  
• Subtle decrease in dexterity
  
• Decreased arm swing on the first-involved side
  
• Soft voice
  
• Decreased facial expression
  
• Sleep disturbances
  
• Rapid eye movement (REM) behavior disorder (RBD; a loss of normal atonia during REM sleep)
  
• Decreased sense of smell
  
• Symptoms of autonomic dysfunction (eg, constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
  
• A general feeling of weakness, malaise, or lassitude
  
• Depression or anhedonia
  
• Slowness in thinkin

Onset of motor signs include the following:

• Typically asymmetric
  
• The most common initial finding is a resting tremor in an upper extremity
  
• Over time, patients experience progressive bradykinesia, rigidity, and gait difficulty
  
• Axial posture becomes progressively flexed and strides become shorter
  
• Postural instability (balance impairment) is a late phenomenon

Nonmotor symptoms

Nonmotor symptoms are common in early Parkinson disease. Recognition of the combination of nonmotor and motor symptoms can promote early diagnosis and thus early intervention, which often results in a better quality of life.

Diagnosis

Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.

Clinical diagnosis requires the presence of 2 of 3 cardinal signs:

• Resting tremor
  
• Rigidity
  
• Bradykinesia
  

Management

The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects.

Symptomatic drug therapy

• Usually provides good control of motor signs of Parkinson disease for 4-6 years
  
• Levodopa/carbidopa: The gold standard of symptomatic treatment
  
• Monoamine oxidase (MAO)–B inhibitors: Can be considered for initial treatment of early disease
  
• Other dopamine agonists (eg, ropinirole, pramipexole): Monotherapy in early disease and adjunctive therapy in moderate to advanced disease
  
• Anticholinergic agents (eg, trihexyphenidyl, benztropine): Second-line drugs for tremor only
  

Treatment for nonmotor symptoms

• Sildenafil citrate (Viagra): For erectile dysfunction
  
• Polyethylene glycol: For constipation
  
• Modafinil: For excessive daytime somnolence
  
• Methylphenidate: For fatigue (potential for abuse and addiction)
  

Deep brain stimulation

• Surgical procedure of choice for Parkinson disease
  
• Does not involve destruction of brain tissue
  
• Reversible
  
• Can be adjusted as the disease progresses or adverse events occur
  
• Bilateral procedures can be performed without a significant increase in adverse events
  

Prognosis

Before the introduction of levodopa, Parkinson disease caused severe disability or death in 25% of patients within 5 years of onset, 65% within 10 years, and 89% within 15 years. The mortality rate from Parkinson disease was 3 times that of the general population matched for age, sex, and racial origin. With the introduction of levodopa, the mortality rate dropped approximately 50%, and longevity was extended by many years. This is thought to be due to the symptomatic effects of levodopa, as no clear evidence suggests that levodopa stems the progressive nature of the disease.

The American Academy of Neurology notes that the following clinical features may help predict the rate of progression of Parkinson disease :
Older age at onset and initial rigidity/hypokinesia can be used to predict (1) a more rapid rate of motor progression in those with newly diagnosed Parkinson disease and (2) earlier development of cognitive decline and dementia; however, initially presenting with tremor may predict a more benign disease course and longer therapeutic benefit from levodopa
A faster rate of motor progression may also be predicted if the patient is male, has associated comorbidities, and has postural instability/gait difficulty (PIGD)
Older age at onset, dementia, and decreased responsiveness to dopaminergic therapy may predict earlier nursing home placement and decreased survival
Patient Education

Patients with Parkinson disease should be encouraged to participate in decision making regarding their condition. In addition, individuals and their caregivers should be provided with information that is appropriate for their disease state and expected or ongoing challenges. Psychosocial support and concerns should be addressed and/or referred to a social worker or psychologist as needed.

Prevention of falls should be discussed. The UK National Institute for Health and Clinical Excellence has several guidance documents including those for patients and caregivers.

Other issues that commonly need to be addressed at appropriate times in the disease course include cognitive decline, personality changes, depression, dysphagia, sleepiness and fatigue, and impulse control disorders. Additional information is also often needed for financial planning, insurance issues, disability application, and placement (assisted living facility, nursing home).

Can Particles in Dairy and Beef Cause Cancer and MS?

In our Western diet, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center(DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.

Acid Radicals 

However, viruses — just like bacteria and parasites — can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pyloriand liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to de Villiers and zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (ie, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.

Viral Progeny 

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, "This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases." They also detected elevated levels of acid radicals in these areas (ie, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said zur Hausen in a speech.

'Breast Milk Is Healthy'

De Villiers and zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have from MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time — around 1 year — the period of incomplete immunocompetence is bridged.

Colon Cancer 

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.

Institutional Skepticism 

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one's health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat — which in no way signifies causality — but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants due to their micronutrients. They further stated that the products are safe for people of all ages.

Association With MS? 

Unperturbed, de Villiers and zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. "The result was electrifying for us."However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (ie, as solar radiation increases). Also, the EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

Magic Mushrooms could replace Anti-depressants!

I started reading this article in the Indepedent with a curious mind! Interest in the potential medical uses for psychedelics, such as “magic mushrooms” and LSD, has rapidly increased in recent years, leading to the opening of the world’s first formal center for psychedelics research in April — and the center’s leader is already prepared to make a bold prediction about the future of psychedelics in medicine. The ideas are bloomed since the cannabis oil became a prescribed medicine recently.

Emotional Release

Carhart-Harris is currently leading a Centre for Psychedelic Research trial to compare the ability of psilocybin, or “magic,” mushrooms and leading antidepressants to treat depression.

He told The Independent that so far, participants are reporting that the psilocybin leaves them feeling like they’ve experienced an emotional “release,” while patients often criticize antidepressants for making them feel like their emotions are “blunted.”

Wishful Thinking

Given the ‘positive’ feedback from study participants and psilocybin mushrooms’ extremely low risk for overdose or addiction, it’s not hard to see why Carhart-Harris is optimistic that doctors will soon be able to use psychedelics to treat patients. Although, we know that the ‘magic’ mushrooms are abundantly available in the streets and self medicating is not uncommon in UK. 

Another psychedelics researcher, James Rucker from King’s College London, isn’t so sure about Carhart-Harris’ timeline (which I’m not comfortable either), telling The Independent that five years is “possible… but only if everything goes to plan, and you know what they say about best-laid plans.”
So next time when you travel through M1,  look out for majestic magic mushroom fields! 

READ MORE: Magic mushrooms could replace antidepressants within five years, says new psychedelic research centre [The Independent]