Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
jo
Basal Ganglia
Consist of Four Nuclei
striatum caudate and putamen globus pallidus substantia nigra subthalamus
The basal ganglia are the principal subcortical components of a family of parallel circuits linking the thalamus with the cerebral cortex
Caudate Circuit
Caudate extends into all lobes of the cortex and receives a large input from association areas of the cortex
Putamen Circuit
Mostly from premotor and supplemental motor cortex to putamen then back to motor cortex.
First described in 1817 by an English physician, James Parkinson, in An Essay on the Shaking Palsy.
The famous French neurologist, Charcot, further described the syndrome in the late 1800s.
Epidemiology of PD
The most common movement disorder affecting 1-2 % of the general population over the age of 65 years.
The second most common neurodegenerative disorder after Alzheimers disease (AD).
Incidence of PD
Age
Prevalence of PD
Age
Epidemiology of PD
May be less prevalent in China and other Asian countries, and in African-Americans. Prevalence rates in men are slightly higher than in women; reason unknown, though a role for estrogen has been debated.
Risk factors of PD
Age - the most important risk factor Positive family history Male gender Environmental exposure: Herbicide and pesticide exposure, metals (manganese, iron), well water, farming, rural residence, wood pulp mills; and steel alloy industries Race Life experiences (trauma, emotional stress, personality traits such as shyness and depressiveness)? An inverse correlation between cigarette smoking and caffeine intake in case-control studies.
Clinical features of PD
Three cardinal features: resting tremor bradykinesia (generalized slowness of movements) muscle rigidity
Clinical features of PD
Resting tremor: Most common first symptom, usually asymmetric and most evident in one hand with the arm at rest.
Bradykinesia: Difficulty with daily activities such as writing, shaving, using a knife and fork, and opening buttons; decreased blinking, masked facies, slowed chewing and swallowing. Rigidity: Muscle tone increased in both flexor and extensor muscles providing a constant resistance to passive movements of the joints; stooped posture, anteroflexed head, and flexed knees and elbows.
Neuropathology of PD
Eosinophilic, round intracytoplasmic inclusions called lewy bodies and Lewy neurites. First described in 1912 by a German neuropathologist - Friedrich Lewy. Inclusions particularly numerous in the substantia nigra pars compacta.
Lewy bodies
Not limited to substantia nigra only; also found in the locus coeruleus, motor nucleus of the vagus nerve, the hypothalamus, the nucleus basalis of Meynert, the cerebral cortex, the olfactory bulb and the autonomic nervous system.
Functional neuroanatomy of PD
Substantia nigra: The major origin of the dopaminergic innervation of the striatum.
Part of extrapyramidal system which processes information coming from the cortex to the striatum, returning it back to the cortex through the thalamus. One major function of the striatum is the regulation of posture and muscle tonus.
Neurochemistry of PD
Late 1950s: Dopamine (DA) present in mammalian brain, and the levels highest within the striatum.
1960, Ehringer and Hornykiewicz: The levels of DA severely reduced in the striatum of PD patients.
PD symptoms become manifest when about 50-60 % of the DA-containing neurons in the substantia nigra and 70-80 % of striatal DA are lost.
Dopamine synthesis
Late 1950s: L-dihydroxyphenylalanine (L-DOPA; levodopa), a precursor of DA that crosses the blood-brain barrier, could restore brain DA levels and motor functions in animals treated with catecholamine depleting drug (reserpine). First treatment attempts in PD patients with levodopa resulted in dramatic but short-term improvements; took years before it become an established and succesfull treatment. Still today, levodopa cornerstone of PD treatment; virtually all the patients benefit.
Does not prevent the continuous degeneration of nerve cells in the subtantia nigra, the treatment being therefore symptomatic.
Inhibition of peripheral COMT by entacapone increases the amount of L-DOPA and dopamine in the brain and improves the alleviation of PD symptoms.
Diagnosis of PD
History and clinical examination Positron Emission Tomography (PET) or Single-photon Emission Computed Tomography (SPECT) with dopaminergic radioligands Exclusion of several causes of secondary Parkinsonism
Summary
1-2 % of the general population over the age of 65 y Lewy bodies and Lewy neurites particularly in the substantia nigra pars compacta dopaminergic neurons projecting to striatum DA levels severely reduced in striatum. Resting tremor, bradykinesia, muscle rigidity Levodopa and other dopaminergic drugs No treatment which would prevent the continuous degeneration of nerve cells in the substantia nigra and resulting striatal DA loss
MCQs
Which circuit in the basal ganglia is thought to be involved in the cognitive control of motor functions? A.Caudate circuit B.Putamen circuit C.Papez circuit D.Nigropallidothalamic circuit ANS: A Chorea and choreiform movement is a sign of dysfunction in which brain region? A.Substantia nigra B.Caudate nucleus and putamen C.Subthalamic nucleus D.Thalamus ANS: B Parkinson's disease is the result of A.Disruption of the putamen circuit B.Loss of GABA input from caudate nucleus and putamen to the substantia nigra C.Loss of dopaminergic input from substantia nigra to the caudate nucleus and the putamen D.Loss of serotonin input from substantia nigra to the thalamus and subthalamus ANS: C
MCQs
Neurological disease associated with the globus pallidus produces which type of symptom? A.Rigidity B.Chorea C.Hemiballismus D.Athetosis ANS: D Which of the following structures is not considered to be part of the basal ganglia? A.Caudate nucleus B.Red nucleus C.Substantia nigra D.Putamen ANS: B Hemiballismus is associated with damage or dysfunction of which of the following structures? A.Thalamus B.Caudate nucleus C.Subthalamus D.Red nucleus ANS: C
Task
Read the case details Identify the keywords Define important terms
Home work
Case Details
A 58-year-old male patient who was a univeristy professor by occupation, was seen by the neurologist He visited the neurologist because for the past 3 months, he was experiencing a recent onset of an intermittent shaking movement involving both his upper limbs that occurs primarily at rest. He also had difficulty in getting out of bed in the mornings But once he got up he carried on with his daily work He also complained of difficulty in turning his body rapidly when someone called him from the back
Key words
A 58-year-old male patient who was a univeristy professor by occupation, was seen by the neurologist He visited the neurologist because for the past 3 months, he was experiencing a recent onset of an intermittent shaking movement involving both his upper limbs that occurs primarily at rest. He also had difficulty in getting out of bed in the mornings But once he got up he carried on with his daily work He also complained of difficulty in turning his body rapidly when someone called him from the back
Questions
What are the presenting symptoms in this patient ? Why do you think he went to a neurologist ? Which parts of the CNS are involved in the control of movement ?
Case details
Neurologic evaluation reveals mild upper limb rigidity in addition to the resting tremor in the upper limbs. The doctor noticed that all the movement of the patient were slow. On further neurological examination, when the patient is asked to walk to and fro his arms do not sway and he finds it difficult to turn around. His blood pressure and vital signs are normal
Key words
Neurologic evaluation reveals mild upper limb rigidity in addition to the resting tremor in the upper limbs. The doctor noticed that all the movement of the patient were slow. On further neurological examination, when the patient is asked to walk to and fro his arms do not sway and he finds it difficult to turn around. His blood pressure and vital signs are normal
Questions
What is rigidity ? (Increased tone of the muscles due to a lesion of the extra pyramidal system) What do you mean by tremor ? What is the neurological term for slowness of movement ? What does the triad of tremor rigidity and bradykinesia suggest ?
Case details
After a detailed history and examination, the neurologist concludes that the patient has features of Parkinsonism.
Keywords
After a detailed history and examination, the neurologist concludes that the patient has features of Parkinsonism.
Questions
What is Parkinsonism ? Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability Which part of the nervous system is involved with parkinsonism ? How does the body perform a smooth, controlled and coordinated movement?
An individual must first be aware of the surrounding environment and his position in space. This information is generated through somatosensory, proprioceptive, and visual sensory inputs to the posterior parietal cortex.
The individual then decides what action is desired. This is accomplished via the parietal and anterior frontal lobes, which are extensively interconnected. These regions are thought to be important for abstract thought and decision making, and hence it is here that decisions about what actions to take are made and their likely outcomes are judged.
A plan must then be constructed to determine how the actions will be carried out. This is performed in the premotor cortex (PMC) and supplemantary motor areas (SMA), where axons from the both the prefrontal and and parietal cortex converge. In this area the signals indicating what actions are desired are converted into signals that indicate how the actions will be perfomed.
Finally, a command to begin the action must be issued and the plan must be implemented. This invloves the primary motor cortex, which, together with the PMC and SMA, contributes most of the axons to the descending corticospinal tract. From this region of the brain signals pass out to the muscles, converting the plan of action into an actual movement.
What are the structures in the brain that regulate and coordinate motor activity ?
Cerebellum Basal ganglia
Cerebellum
The main function of the cerebellum is the coordination of motor activities. Commands to initiate movement come from the somatomotor cerebral cortex, but the cerebellum fine-tunes motor control, giving smoothness of motion and exactness of positioning. The cerebellum makes comparisons of internal and external feedback signals to correct ongoing movements. Lesions of the cerebellum result in movements that are jerky and that overshoot or undershoot their intended mark. The cerebellum is the site to ensure well-timed and co-ordinated movements and sequences.
Basal Ganglia
The term basal ganglia relate to a set of nuclei that are located deep in the hemispheres. The basal ganglia are involved in the regulation of cortically initiated motor activity, which if disturbed leads to some form of movement disorder
the basal ganglia receive inputs from the cerebral cortex , the inputs go onward to the various parts of the basal ganglia and then signals go back to the cerebral cortex via the thalamus. What could be the purpose of this loop? Evidently the basal ganglia function to maintain the muscle tone needed to stabilize joint position (as, for example, holding a glass of water while talking) or to inhibit muscle tone during the initiation of movement.
Interruption of the feedback loops of the basal ganglia by damage to one of its structures results in the uncontrollable oscillations manifested as tremors or as other movement disorders.
Home work
What are the parts of the basal ganglia ? What are the functions of basal ganglia ? What are the types of movement disorders ? What are the causes of Parkinsonism ? List the various clinical signs of parkinsonism. What is Levo Dopa ?