UNIVERSIDAD NACIONAL DE

JAÉN

CARRERA PROFESIONAL DE TECNOLOGÍA MÉDICA

FARMACOLOGIA Y TOXICOLOGIA

Ciclo: V

Semana :03

Docente: JOSE CELSO PAREDES CARRANZA

Integrantes:

❖ ELVIS YAMIR AYALA SALAZAR

❖ BRAHIAN ANDERSON GARCIA OBLITAS
❖ RIXER CONDEZO HUAMAN
❖ CHRISTIAN PALOMINO FERNANDEZ
❖ CLENDY YUDITH RIMAPA GUERRERO
❖ MARJHURI LISDEY RIVAS ARÉVALO
Introduction, epidemiology and diagnosis of Parkinson's
disease
ABSTRACT
Parkinson's disease is a neurodegenerative disorder that has multiple motor and non-motor
manifestations. The pathological process begins years or decades before the onset of non-motor
symptoms, at which time other symptoms develop that very often precede the clinical onset. Although
much progress has been made in understanding the pathogenesis and in recognizing the numerous
non-motor manifestations, diagnosis continues to focus on the motor syndrome or parkinsonism. This
chapter presents an update on recent data related to the increase in the global prevalence of the
disease, as well as the diagnosis based on the new criteria defined by the International Society of
Movement Disorders in 2015, which are based on the central criteria. but they take into account red
flags for the possible existence of other parkinsonisms, absolute exclusion criteria and support criteria,
the latter recognizing the usefulness of non-motor symptoms and some paraclinical aids to support in
vivo diagnosis.

KEY WORDS: Parkinson's disease; Consensus; Neurodegeneration; Prevalence; Epidemiology;

Diagnosis (DeCS).

DEFINITION
Idiopathic PD is a neurodegenerative condition, clinically characterized by the presence of a "typical"
motor phenotype (parkinsonism), with sustained and consistent response to levodopa, in addition to
non-motor symptoms that are often present years or decades before the phenotype. Motor The onset
of motor symptoms is usually asymmetric and this asymmetry is maintained throughout the course of
the disease. Non-motor symptoms include sleep disturbances (fragmentation, daytime sleepiness, and
rapid eye movement sleep behavior disorder or REM-CT), cognitive symptoms (executive dysfunction,
recall deficits, dementia, and hallucinations), mood disturbances, autonomic dysfunction (orthostatic
hypotension, urogenital dysfunction, constipation and hyperhidrosis), as well as sensory-perceptual
disorders (the most prominent being hyposmia) and pain

Histopathologically, the main features of the disease are moderate to severe neuronal loss in the
substantia nigra pars compacta (SNpc) and the presence in most cases of alpha-synuclein deposits in
the form of Lewy bodies and Lewy neurites. Pathologically, other areas of the nervous system and
various neurotransmitter systems are also affected, accounting for many of the non-motor symptoms
of the disease.

EPIDEMIOLOGY
It is the second most common neurodegenerative disease after Alzheimer's disease. In 2016, it was
estimated that 6.1 million people in the world suffered from the disease, which represented an
increase of more than double compared to the 1990 figure (2.5 million). In 2040 it is estimated that
there will be around 17 million affected. This makes Parkinson's disease the fastest growing of all
neurological diseases worldwide according to the Global Burden of Disease study.

Age is the risk factor most consistently associated with PD. There is a prevalence peak between 85 and
89 years (1.7% in men and 1.2% in women) and a decrease from this age.
Disease risk appears to be determined by complex interactions between factors in the individual (such
as age and the presence of certain genetic polymorphisms or mutations) and factors in the
environment. Regarding genetic risk factors, the one with the most robust evidence is the presence of
mutations in the GBA gene (which codes for the lysosomal enzyme beta-glucocerebrosidase). Other
identified genes are related to monogenic forms of the disease (such as LRRK-2 and SNCA). A recent
meta-analysis involving more than 13,000 patients with Parkinson's disease found an association
between 24 loci and disease risk modification.

CLINICAL MANIFESTATIONS

Parkinson's disease is a complex entity that encompasses various manifestations related to the
compromise of multiple neurotransmitter systems. Despite the advances made in understanding the
pathogenesis and pathophysiology of the disease, in addition to the identification of a premotor phase
in which symptoms such as constipation, depression and REM-CT appear, the diagnosis continues to
be focused on in parkinsonian syndrome and until now it is not possible to do it before the onset of
motor symptoms.

Once the motor symptoms appear, there is already a loss of dopaminergic neurons of the SNpc of
between 50 and 80 °%. The pathological progression model of the disease proposed by Braak et al.
indicates that the neurodegenerative process enters the central nervous system through the nerve
endings of the olfactory bulb or the enteric nervous system. Subsequently, it compromises caudal
structures such as the dorsal motor nucleus of the vagus nerve and spreads rostrally to finally
compromise the cerebral cortex.

The prodromal phase of the disease, which occurs in a fraction of patients, is characterized by the
presence of depression, constipation, smell disorders (hyposmia) and sleep (REM-TC). Once motores
symptoms become manifest and diagnosis is made, there is a substantial and consistent response to
levodopa that lasts an average of three to five years before the onset of treatment-related motor
complications, including motor fluctuations and dyskinesias.

DIAGNOSIS

Advances in the knowledge of the pathophysiology and the recognition of non-motor symptoms have
meant that in recent years the conception about the definition of the disease has changed.

A validation study of the 2015 MDS criteria was recently published and found a diagnostic accuracy of
92%, sensitivity of 94.5%, and specificity of 88.5% (compared to the reference standard which is
diagnosis by a clinician). with more than 10 years of experience in diagnosing Parkinson's disease).

OFFICIAL CRITERIA OF THE INTERNATIONAL SOCIETY OF PARKINSON AND

MOVEMENT DISORDERS FOR THE CLINICAL DIAGNOSIS OF PARKINSON'S
DISEASE

The new criteria emphasize:

A. MOTOR SYNDROME AS A CENTRAL FEATURE

The central feature is the motor syndrome by which PD is clinically defined. However, non-motor
symptoms are present in many patients and can often dominate the clinical presentation. Many of
these manifestations have now been incorporated into the diagnostic criteria.

The criteria use two steps for diagnosis:

 1. Establish the presence of parkinsonism, which is defined by bradykinesia in combination with
either of the following: tremor at rest or rigidity, or both.
2. Define with the other criteria if this parkinsonism is attributed to PD.

B. REFERENCE STANDARD: EXAMINATION BY AN EXPERT

Between 75 and 95% of patients diagnosed with PD by experts have been confirmed by autopsy. The
precise diagnosis varies considerably according to the duration of the disease, age, the expertise of the
physician, and the evolution in understanding of the disease. The 2015 MDS criteria were designed to
minimize diagnostic errors. Until validated diagnostic markers are available, expert clinical opinion will
follow the gold standard for diagnosis in life.

C. LEVELS OF CERTAINTY
The 2015 MDS criteria include different levels of diagnostic certainty. These are:

1. Clinically established Parkinson's disease: The probability of having PD in patients meeting

these criteria is expected to be 90%.
2. Clinically Probable Parkinson's Disease: The goal for this category is for at least 80% of patients
diagnosed as probable PD to have a correct diagnosis, balancing sensitivity and specificity.

CRITERIA FOR PARKINSON'S DISEASE

Criteria for Parkinsonism

The prerequisite for applying the MDS 2015 criteria is the diagnosis of parkinsonism, which is based on
three cardinal motor manifestations: bradykinesia in combination with tremor at rest and/or rigidity.
These characteristics must be clearly demonstrated and must not be attributed to confounding factors.

DEFINITION OF CARDINAL MANIFESTATIONS OF PARKINSONISM

Bradykinesia: is defined as slowing of movement and decrease in amplitude or speed, or

blockages in the continuity of movement.

Rigidity: it is a resistance to passive movement of the limbs with the patient in a relaxed position,
which can be in a cogwheel or lead pipe.

Resting tremor: 4 to 6 Hz in the fully relaxed limb, which is suppressed during initiation of
movement. A parkinsonian resting tremor may be seen in the hand with prolonged posture (re-
emergent tremor). However, for this criterion to apply, the presence of tremor at rest must be
demonstrated.

Although postural instability is a characteristic of parkinsonism, it is not part of the 2015 MDS criteria
for parkinsonism caused by PD. It often occurs in late stages, but its early presence suggests an
alternative diagnosis.
REFERENCES

1. Kalia LV, Lang AE. Parkinson's hisses. Lancet. 2015;386(1):896-912. Available at:
http://dx.doi.org/10.1016/S0140-6736(14)61393-3 [ Links ]
2. Parkinson J. An Essay on the Shaking Palsy [e-book version]. J Neuropsychiatry Clin
Neurosci. 1817;14(2):223-36. Available at:
http://www.gutenberg.org/files/23777/23777-h/23777-h.htm [ Links ]