Basal Ganglia

Chorea

It means literally "dance" and is applied to movement disorders characterized nearly continuous involuntary movements that have a fluid or jerky, constantly varying quality. In mild cases, low-amplitude chorea may be mistaken for fidgeting or restless movements of the extremities, face, or trunk. Choreic movements are often incorporated into voluntary movements in an attempt to conceal their occurrence. In severe cases, larger-amplitude movements resemble frantic "break dancing," occurring constantly, interrupting voluntary movements, and increasing during distraction or during ambulation. Chorea can involve proximal and distal extremities, the trunk, neck, face, and respiratory muscles.

Parkinson's Disease (Paralysis Agitans)

It is a sporadic disorder of unknown etiology that occurs worldwide. The usual age of onset is between 40 and 70 years. Agitans means shaking, hence, also called shaking palsy. It usually have the classic triad of Resting tremor, bradykinesia, and lead pipe/cogwheel rigidity, accompanied by postural instability that causes an unsteady gait.

Athetosis

It is characterized by writhing, twisting movements of the limbs, face, and trunk that sometimes merge with faster choreic movements, giving rise to the term choreoathetosis. Important causes include perinatal hypoxia involving the basal ganglia, kernicterus caused by severe neonatal jaundice, Wilson's disease, ataxia, telangiectasia, Huntington's disease, and antipsychotic or anti-emetic medications.

Basal Ganglia

A set of subcortical structures that directs intentional movements structures in the forebrain that help to control movement

Components of Basal Ganglia

Caudate nucleus Putamen Globus pallidus External Segment Internal Segment Subthalamic nucleus Substantia nigra Pars Compacta Pars Reticulata

Lesion of caudate nucleus

Delayed alternation & disrupt performance on tests involving object reversal.

Pathways of the basal ganglia

Direct and indirect

Lesion of head of left caudate nucleus

Dysarthric aphasia (difficulty in articulating words)

Kernicterus

Hemolytic disease of newborn → ↑ indirect bilirubin → bilirubin crosses blood brain barrier → damages globus pallidus → death

connections of basal ganglia

Inputs Arrive at the Striatum Outputs Arise from the Internal Globus Pallidus and the Substantia Nigra Pars Reticulata

Disorders of Basal Ganglia

Movements disorders Bradykinesia- slowed movements Hypokinesia -decreased amount of movements. Akinesia -absence of movement." These terms are traditionally reserved for localizations at levels higher than the upper motor neurons. Rigidity Increased resistance to passive movement of a limb is called rigidity. It is often present in disorders that cause bradykinesia or dystonia. Rigidity caused by basal ganglia disorders tends to be more continuous throughout attempts to bend the limb, and it has therefore been called plastic,waxy, or lead pipe rigidity. Dystonia The patient assumes abnormal, often distorted positions of the limbs, trunk, or face that are more sustained or slower than in athetosis. It can be generalized, unilateral, or focal. Focal dystonias include torticollis, which involves the neck muscles; blepharospasm, which involves the facial muscles around the eyes; spasmodic dysphonia, which involves the laryngeal muscles; and writer's cramp. These disorders are presumed to be caused by basal ganglia dysfunction, although usually no focal lesion is found. Many cases of dystonia respond well to injection of small amounts of botulinum toxin("Botox") into the affected muscles, which needs to be repeated every few months.

Ballism

Movements of the proximal limb muscles with a larger-amplitude, more rotatory or flinging quality than chorea are referred to as ballism or ballismus. The most common type is hemiballismus, in which there are unilateral flinging movements of the extremities contralateral to a lesion in the basal ganglia. The classic cause is a lacunar infarct of the subthalamic nucleus, which leads to decreased pallidal inhibition of the thalamus

Pathological Features of Parkinson's disease

Pathologically, there is loss of pigmented dopaminergic neurons in the substantia nigra pars compacta, causing the substantia nigra to appear pale to the eye on cross section. Remaining dopaminergic neurons often contain characteristic cytoplasmic inclusions called Lewy bodies, which are eosinophilic, contain ubiquitin and α-synuclein, and have a faint halo.

Caudate nucleus

Plays important role in cognitive processes because of its interconnections with orbitofrontal & dorsolateral prefrontal lobe.

Globus pallidus

Provides appropriate muscle tone for performance of skilled movements.

Substantia nigra

center for coordination of impulses essential for skilled movements.

Tics

A sudden brief action that is preceded by an urge to perform it and is followed by a sense of relief is called a tic. Motor tics usually involve the face or neck and, less often, the extremities. Vocal tics can be brief grunts, coughing sounds, howling or barking-like noises, or even more elaborate vocalizations that sometimes include obscene words (coprolalia). Tic disorders make up a spectrum ranging from transient single motor or vocal tics of childhood to Tourette's syndrome (also known as Gilles de la Tourette's syndrome), which is characterized by persistent motor and vocal tics.

Huntington's Disease

An autosomal dominant neurodegenerative condition characterized by a progressive, usually choreiform movement disorder, dementia, and psychiatric disturbances, ultimately leading to death. Clinical onset is usually between 20 and 40 years of age. The disease is progressive and usually leads to a fatal outcome within 15-20 years. The initial symptoms may consist of either abnormal movements or intellectual changes, but ultimately both occur. Gradual onset and progression of chorea and dementia or behavioral change. Cause Due to degeneration of GABAergic striatonigral pathway. GABAergic & cholinergic neurons are lost in the striatum.

Clinical Features of Huntington's disease

Chorea: Rapid, involuntary & dancing movements Loss of GABAergic neurons in striatum → removes inhibitory influence on globus pallidus → reduces activities in thalamic nucleus Dementia: Due to simultaneous & progressive loss of cholinergic neurons in cerebral cortex The earliest mental changes are often behavioral, with irritability, moodiness, antisocial behavior, or a psychiatric disturbance, but a more obvious dementia subsequently develops. Gradually, speech is slurred in Huntington disease The pathologic hallmark of Huntington's disease is progressive atrophy of the striatum, especially involving the caudate nucleus. No definite treatment Disease is progressively fatal

Basal Nuclei Grouping

Corpus Striatum Caudate nucleus Putamen Globus Pallidus Neostriatum or Striatum Caudate nucleus Putamen Lentiform Nucleus Putamen Globus Pallidus Paleostriatum Globus Pallidus Externa Globus Pallidus Interna

Clinical Features of Parkinson's disease

Hypokinetic Movements Akinesia and Bradykinesia Decreased associated movement: no swinging of arms during walking Masklike face: no facial expression during speaking. Hyperkinetic Movements Rigidity: Motor neuron discharge is ↑ed in both agonists & antagonists. Lead pipe rigidity; sometimes cogwheel rigidity is also seen. Posture is that of flexion attitude. Tremor: Pill-rolling tremors (rhythmic contraction of thumb over first two fingers @ 6-8 times/sec) Present at rest but disappears during activity (resting or static tremor). Festinant Gait (shuffling gait): Patient is bent forward (Stooped), & walks quickly with short steps as if trying to catch up center of gravity or preventing himself from falling down. If he is suddenly pulled backwards, he begins to walk backwards & is unable to stop himself (retropulsion). Tendon jerks: more difficult to elicit due to rigidity

Cause of Parkinson's Disease

Idiopathic Drugs: Reserpine (reduce dopamine stores in appropriate nerve endings); Phenothiazine (blocks D2 dopamine receptor in neostriatum) MPP: Methyl-phenyl-tetrahydropyridinum (MPTP), found in contaminated low quality street heroine, is converted by MAO-B into methyl-phenyl-pyridinum (MPP), which accumulates in dopaminergic neurons of basal ganglia & destroy them. Exposure to certain toxins (eg, manganese dust, carbon disulfide) and severe carbon monoxide poisoning may lead to parkinsonism.

Indirect pathway of basal ganglia

It begins with the Striatum being excited by the Cortex (just like the direct pathway). Then Striatal neurons send inhibitory input to the external segment of the Globus Pallidus using the neurotransmitters GABA or Enkephalin. The Globus Pallidus external segment usually sends inhibitory input to the Subthalamic Nucleus using GABA, but if it is inhibited by the Striatum then it is unable to inhibit the Subthalamic nucleus leaving it free to fire. The Subthalamic Nucleus being uninhibited sends the only purely excitatory (Glutamate)input within the Basal Ganglia pathways to the Globus Pallidus internal segment and the Substantia Nigra pars reticulata. These structures then inhibit the VA and VL of the Thalamus making it unable to send excitatory input to the Cortex and thus indirectly inhibiting the Motor Cortices, which inhibits movement. Cholinergic neurons found within the striatum have the opposite effect. Acetylcholine (Ach)drives the indirect pathway, decreasing cortical excitation.

Direct pathway of basal ganglia

It begins with the Striatum being excited by the Cortex. The Striatum then inhibits the internal segment of the Globus Pallidus and the Substantia Nigra pars reticulata using the neurotransmitters GABA or Substance P (Sub P). When these structures are inhibited they cannot inhibit the Thalamus rendering it free to fire and send excitatory input up to the Cortex, which facilitates movement.

Functions of basal ganglia

Planning & Programming of movements by preventing oscillations Subthalamic nuclei provide excitatory input to globus pallidus Globus pallidus sends fibers back to subthalamic nuclei Activity of basal ganglia is more during slow, steady damp movement & is silent during, rapid, saccadic movement. Inhibits the stretch reflex (muscle tone) by stimulation of inhibitory motor cortex and Inhibitory reticular formation Neostriatum regulates subconscious gross movements occurring in groups of the muscles. Caudate nucelus plays important role in cognitive processes because of its interconnections with orbitofrontal & dorsolateral prefrontal lobe. Globus pallidus provides appropriate muscle tone for performance of skilled movements. Substantia nigra is center for coordination of impulses essential for skilled movements. Control of normal automatic & associated movements such as swinging of arms during walking (initiated by motor cortex area 6).

Wilson's disease

Progressive hepatolenticular degeneration It results from an abnormality of copper metabolism, causing the accumulation of copper in the liver and basal ganglia. Feature Characterized by personality changes, tremor, dystonia, and athetoid movements. A thin brown ring a round the outer cornea, the Kayser-Fleischer ring, may be present and aid in the diagnosis. Low plasma ceruloplasmin (plasma copper binding protein) → increase copper content in substantia nigra. Severe degeneration of lentiform nucleus with cirrhosis of liver.

Neostriatum

Regulates subconscious gross movements occurring in groups of the muscles.

Treatment for Parkinson's disease

Replacement of dopamine: Dopamine cannot cross blood brain barrier. Levo-DOPA, a precursor of dopamine, that easily crosses BBB is the drug of choice. Dopamine agonists - e.g., Bromocriptine are also used. Anticholinergics: Alteration in the ratio of dopamine & acetylcholine plays an important role in Parkinson's disease. Injection of Anticholinergics → ↓es Ach concentration in basal ganglia → reestablishes Ach - dopamine ratio → improves the symptoms Selegilin (Deprenyl): Inhibits MAO-B & prevents formation of MPP from MPTP. Amantadine: Antiviral medication is also effective in treating Parkinson's disease due to its anticholinergic and antiglutamatergic effects and also acts by increasing dopamine output from intact nerve terminals. COMT (catechol-O-methyl transferase) Inhibitor: This enzyme is involved in degrading neurotransmitters. e.g. Entacapone, tolcapone, and nitecapone

Genetic factors for Parkinson's disease

SNCA (synuclein, alpha non A4 component of amyloid precursor): SNCA makes the protein alpha-synuclein. In brain cells of individuals with Parkinson's disease, this protein aggregates in clumps called Lewy bodies. Mutations in the SNCA gene are found in early-onset Parkinson's disease. PARK2 (Parkinson's disease autosomal recessive, juvenile 2): The PARK2 gene makes the protein parkin. Mutations of the PARK2 gene are mostly found in individuals with juvenile Parkinson's disease. Parkin normally helps cells break down and recycle proteins. PARK7 (Parkinson's disease autosomal recessive, early onset 7): PARK7 mutations are found in early-onset Parkinson's disease. The PARK7 gene makes the DJ-1 protein, which may protect cells from oxidative stress. PINK1 (PTEN-induced putative kinase 1): Mutations of this gene are found in early-onset Parkinson's disease. The exact function of the protein made by PINK1 is not known, but it may protect structures within the cell called mitochondria from stress. LRRK2 (leucine-rich repeat kinase 2): LRRK2 makes the protein dardarin. Mutations in the LRRK2 gene have been linked to late-onset Parkinson's disease.

Surgical Treatment of Parkinson's disease

Transplantation of adrenal: Transplantation of adrenal medulla from one of the adrenal gland of the patient into his basal ganglia helps in regenerating dopaminergic neurons. Implantation of fetal basal ganglia: Implantation of tissue from fetal basal ganglia into the basal ganglia of the patient. Transplantation of Glomus cells: Recently, isolated glomus cells from carotid body transplanted into basal ganglia has been found to be encouraging. Deep brain stimulation (DBS) is a surgical procedure used to treat several disabling neurological symptoms—most commonly the debilitating motor symptoms of PD, such as tremor, rigidity, stiffness, slowed movement, and walking problems. At present, the procedure is used only for individuals whose symptoms cannot be adequately controlled with medications. Deliver electrical stimulation to specific areas in the brain that control movement, thus blocking the abnormal nerve signals that cause PD symptoms.