Carlos Vendrell
Clinical Neuroscience – Best notes ever 2
1. Parkinson’s disease
Parkinson’s disease (PD) is a complex and gradually progressive neurodegenerative condition.
PD is the second most common neurodegenerative disease after Alzheimer’s disease (AD).
Epidemiology
Prevalence 1/800
Incidence 1/8000
This percentages increase with aging (1% prevalence in a population > 65 years, being the mean
age of onset 70). It’s a disease more prevalent in males than females, sex dependent. With an
aging population, both the prevalence and incidence of PD are expected to increase by more
than 30% by 2030.
Risk factors that make the coming generations more
likely to develop Parkinson:
- Older population (longer life)
- Addictive behaviour as daily ingest of alcohol,
caffeine...
- Repetitive head injury
- Pesticides exposure
- Genetic risk factors
They are risk factors but not always
directly related, people exposed to
them not always present PD.
Diagnosis
Clinical symptoms develop very slow in the disease. Mild motor complains, and symptoms can
be detected at the early stage. (Keep in mind that these symptoms not always point to PD, there
are many diseases with similar clinical profile, causing parkinsonism, not Parkinson disease, and
most of the times patients are not treated directly by a neuropsychiatric giving way to
misdiagnosis).
• Shoulder pain
• Rest tremor
• Smaller handwriting
• Walking problems
• Hypomimia: Lost of facial expression. They blink less often, have the mouth open even
when not talking
1
,Carlos Vendrell
Other clinical clues (even prior of the motor symptoms):
• Constipation
• Olfactory loss
• Change of mood
• REM sleep behaviour (movements when sleeping/dreaming)
The main symptoms and the ones that the patient may present to be diagnosed with Parkinson
are:
• Bradykinesia: Slow motor movements. Decrement in
amplitude and frequency
Tested asking the patient to do three different motor exercises:
- Touch repetitively the thumb with the index finger
- Open and close the hand
- Turn the hand as you were changing a light bulb
Observe impairments and how fast the patient makes these movements. No movement of any
other part of the body when performing these tasks, like a statue, is also a sign for diagnosis
(hypokinesia).
• Rigidity: Stiffness. Velocity independent, resistance to passive movement.
• Resting tremor: Frequently in resting limb and as re-emergent tremor in the active limb
(that means that the tremor stops when the patient is performing the task, but when
the activity stops the tremor appears again). Keep in mind that other diseases cause
tremor but only a few cause RESTING tremor (i.e. medication side-effect). Tremor
sometimes interfere with the bradykinesia tests.
In all the diagnostic tests patients are asked to perform some mental activity earlier than the
motor task (i.e. mention names starting with a given letter) in order to distract them and then
the bradykinesia and tremor are analysed.
The main problem in the diagnosis of PD is that there are no reliable biomarkers or genetic
screenings of the disease. Diagnosis is basically based on symptomatic problems.
Supportive criteria
• Positive effect medication
• Loss of olfaction
• Resting tremor
Exclusion criteria (sign that the symptoms are related with a different reason than PD)
• Cerebellar abnormalities
• Downward vertical gaze palsy
• Frontotemporal dementia or primary progressive aphasia
• Lower limb parkinsonism (> 3 yr)
• Drug-induced parkinsonism
• Absence of drug response
• Cortical sensory loss
• Normal presynaptic dopaminergic imaging
• Alternative condition
2
,Carlos Vendrell
Red flags (Symptoms that differentiate Parkinsonism symptoms from really PD)
• Rapid progression of gait impairment (wheelchair)
• Complete absence of progression of motor symptoms (5 yr)
• Early bulbar dysfunction
• Inspiratory respiratory dysfunction
• Severe autonomic failure early in disease
• Recurrent falls early in disease
• Disproportionate anterocollis, contractures
• Absence of non-motor symptoms (in 5 yrs)
• Pyramidal tract signs
• Symmetric parkinsonism
Clinical established PD:
• Absence of absolute exclusion criteria
• At least two supportive criteria
• No red flags
Clinical probable PD:
• Absence of absolute exclusion criteria
• Presence of red flags counterbalanced by supportive criteria (no more than 2 red flags)
Although not done very often, another diagnosis test is imaging to check for possible brain
tumours (MRI). Patient clinical and health profile and previous tests are known so if there is a
tumour it would have probably be discovered already. DAT-SPECT is also an alternative
technique for diagnosis, look at dopaminergic decrease by scan (dopaminergic regions are
dyed/stained).
Differential diagnosis
Examples of other diseases or causes of parkinsonism:
• Essential tremor (active, not resting or passive)
• Drug induced parkinsonism
• Vascular parkinsonism
• Atypical parkinsonism
- Multiple system atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Dementia with Lewy Bodies (DLB)
- Cortical basal degeneration (CBD)
3
, Carlos Vendrell
Braak staging
Spread of aSyn from the
brainstem to other cortical
regions being the olfactory
tract one of the first regions
affected and therefore, the
loss of smell capacity, one of
the first symptoms.
Non-motor symptoms
Historically PD was associated with ONLY motor symptoms but there are also non-motor and
neurological impairments. That's because not only dopamine is altered, also other
neurotransmitters. Some non-motor symptoms occur even at early stages of the disease as sleep
disorders, depression or hallucionations.
Neuropsychiatric dysfunction
• depression
• anxiety
• cognitive disturbances/dementia
• psychosis /visual hallucinations (partially increased by medication)
• impulse control disorders
Sleep disturbance (medication also contributes increasing these impairments)
• insomnia
• restless legs
• REM-sleep behaviour disorder
• excessive daytime sleepiness
4
Clinical Neuroscience – Best notes ever 2
1. Parkinson’s disease
Parkinson’s disease (PD) is a complex and gradually progressive neurodegenerative condition.
PD is the second most common neurodegenerative disease after Alzheimer’s disease (AD).
Epidemiology
Prevalence 1/800
Incidence 1/8000
This percentages increase with aging (1% prevalence in a population > 65 years, being the mean
age of onset 70). It’s a disease more prevalent in males than females, sex dependent. With an
aging population, both the prevalence and incidence of PD are expected to increase by more
than 30% by 2030.
Risk factors that make the coming generations more
likely to develop Parkinson:
- Older population (longer life)
- Addictive behaviour as daily ingest of alcohol,
caffeine...
- Repetitive head injury
- Pesticides exposure
- Genetic risk factors
They are risk factors but not always
directly related, people exposed to
them not always present PD.
Diagnosis
Clinical symptoms develop very slow in the disease. Mild motor complains, and symptoms can
be detected at the early stage. (Keep in mind that these symptoms not always point to PD, there
are many diseases with similar clinical profile, causing parkinsonism, not Parkinson disease, and
most of the times patients are not treated directly by a neuropsychiatric giving way to
misdiagnosis).
• Shoulder pain
• Rest tremor
• Smaller handwriting
• Walking problems
• Hypomimia: Lost of facial expression. They blink less often, have the mouth open even
when not talking
1
,Carlos Vendrell
Other clinical clues (even prior of the motor symptoms):
• Constipation
• Olfactory loss
• Change of mood
• REM sleep behaviour (movements when sleeping/dreaming)
The main symptoms and the ones that the patient may present to be diagnosed with Parkinson
are:
• Bradykinesia: Slow motor movements. Decrement in
amplitude and frequency
Tested asking the patient to do three different motor exercises:
- Touch repetitively the thumb with the index finger
- Open and close the hand
- Turn the hand as you were changing a light bulb
Observe impairments and how fast the patient makes these movements. No movement of any
other part of the body when performing these tasks, like a statue, is also a sign for diagnosis
(hypokinesia).
• Rigidity: Stiffness. Velocity independent, resistance to passive movement.
• Resting tremor: Frequently in resting limb and as re-emergent tremor in the active limb
(that means that the tremor stops when the patient is performing the task, but when
the activity stops the tremor appears again). Keep in mind that other diseases cause
tremor but only a few cause RESTING tremor (i.e. medication side-effect). Tremor
sometimes interfere with the bradykinesia tests.
In all the diagnostic tests patients are asked to perform some mental activity earlier than the
motor task (i.e. mention names starting with a given letter) in order to distract them and then
the bradykinesia and tremor are analysed.
The main problem in the diagnosis of PD is that there are no reliable biomarkers or genetic
screenings of the disease. Diagnosis is basically based on symptomatic problems.
Supportive criteria
• Positive effect medication
• Loss of olfaction
• Resting tremor
Exclusion criteria (sign that the symptoms are related with a different reason than PD)
• Cerebellar abnormalities
• Downward vertical gaze palsy
• Frontotemporal dementia or primary progressive aphasia
• Lower limb parkinsonism (> 3 yr)
• Drug-induced parkinsonism
• Absence of drug response
• Cortical sensory loss
• Normal presynaptic dopaminergic imaging
• Alternative condition
2
,Carlos Vendrell
Red flags (Symptoms that differentiate Parkinsonism symptoms from really PD)
• Rapid progression of gait impairment (wheelchair)
• Complete absence of progression of motor symptoms (5 yr)
• Early bulbar dysfunction
• Inspiratory respiratory dysfunction
• Severe autonomic failure early in disease
• Recurrent falls early in disease
• Disproportionate anterocollis, contractures
• Absence of non-motor symptoms (in 5 yrs)
• Pyramidal tract signs
• Symmetric parkinsonism
Clinical established PD:
• Absence of absolute exclusion criteria
• At least two supportive criteria
• No red flags
Clinical probable PD:
• Absence of absolute exclusion criteria
• Presence of red flags counterbalanced by supportive criteria (no more than 2 red flags)
Although not done very often, another diagnosis test is imaging to check for possible brain
tumours (MRI). Patient clinical and health profile and previous tests are known so if there is a
tumour it would have probably be discovered already. DAT-SPECT is also an alternative
technique for diagnosis, look at dopaminergic decrease by scan (dopaminergic regions are
dyed/stained).
Differential diagnosis
Examples of other diseases or causes of parkinsonism:
• Essential tremor (active, not resting or passive)
• Drug induced parkinsonism
• Vascular parkinsonism
• Atypical parkinsonism
- Multiple system atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Dementia with Lewy Bodies (DLB)
- Cortical basal degeneration (CBD)
3
, Carlos Vendrell
Braak staging
Spread of aSyn from the
brainstem to other cortical
regions being the olfactory
tract one of the first regions
affected and therefore, the
loss of smell capacity, one of
the first symptoms.
Non-motor symptoms
Historically PD was associated with ONLY motor symptoms but there are also non-motor and
neurological impairments. That's because not only dopamine is altered, also other
neurotransmitters. Some non-motor symptoms occur even at early stages of the disease as sleep
disorders, depression or hallucionations.
Neuropsychiatric dysfunction
• depression
• anxiety
• cognitive disturbances/dementia
• psychosis /visual hallucinations (partially increased by medication)
• impulse control disorders
Sleep disturbance (medication also contributes increasing these impairments)
• insomnia
• restless legs
• REM-sleep behaviour disorder
• excessive daytime sleepiness
4
