2. Basal Nuclei Connections And Clinical Correlations

3. Clinical Case David is a 66-year-old man, previously healthy, who was brought to a neurologist by his daughter because of increasing difficulty in walking. His daughter noticed that for the past year, he had difficulty getting out of a chair and took a lot of time to begin to walk. When he did walk, he walked with a slow, shuffling gait. In addition, she had noticed some changes in his face, and that he had been drooling excessively. His signature on checks became progressively smaller from the beginning of his name to the end, and he had developed a new tremor. She brought him in to make sure this wasn’t just “aging.” The neurologist examined David and noticed immediately that David facial expression was masklike, with few eye blinks. When asked to write a sentence, the letters became progressively smaller toward the end of the sentence

4. Case Cont… His speech was soft and monotonous, and he had a slow, resting pill-rolling tremor in both of his hands. He had very little spontaneous movement, and his arms, legs, and trunk were stiff. When the neurologist tried to flex his arm, he felt many catches, similar to a cogwheel. There was no weakness, sensory problems, or abnormalities in his reflexes. When asked to walk, David took many tries to rise from his chair. When he finally stood up, his posture was stooped and flexed. His gait was slow, his feet shuffled when he walked, and his arms didn’t swing with his steps. The neurologist told David daughter that she was correct that this wasn’t aging and explained to her all of the details about a new medication that David needed to take.

5. Basal Ganglia Gross Features It is a nuclear mass located within the depths of each cerebral hemisphere. – Corpus Striatum – Claustrum – Amygdaloid body The corpus striatum is the largest component of the basal ganglia. Divided into three components. It includes the caudate nucleus, the putamen and the globus pallidus. The caudate nucleus (CD) is a large C- shaped grey matter located medial to the internal capsule and related throughout its length to the surface of the lateral ventricle.

6. Basal Ganglia Gross Features It has an head that bulges into the lateral wall of the frontal horn of the lateral ventricle. The head tapers to form the body located along the lateral wall of the ventricle. The body in turn becomes further (Continued) attenuated to form the tail which courses along the roof of the temporal horn of the ventricle and terminates at the amygdaloid nucleus. Amygdaloid Nu

7. Basal Ganglia Gross Features The PU and CD together comprise the neostriatum (neo = new) which is sometimes simply abbreviated striatum. Histologically, the structure of the CD and PU are similar. They contain the inhibitory neurotransmitter gamma-amino butyric acid (GABA).

8. Basal Ganglia Gross Features The paleostriatum (paleo = ancient ) or "pallidum" is the forerunner of the mammalian corpus striatum and consists of the globus pallidus (GP) only. The GP is situated medial to the putamen and is separated from it by a thin lamina of myelinated fibers called the external medullary lamina. A similar lamina (medial medullary lamina) divides the GP into a lateral or external division (GPe) and a medial or internal (GPi) division, each of which has its own peculiar set of connections. The GP is traversed by numerous myelinated fibers which give it its characteristic pale appearance in stained sections and from which its name derives.

9. Basal Nuclei Connections

12. Dopamine and Cholinergic Effect

13. Basal Ganglia Connections Supplementary Motor Area (SMA) Primary (M I) THALAMUS (VLo, VApc, CM) STRIATUM(Putamen) PALLIDUM(GPi) pyramidal tract tract LMN

14. Basal Ganglia Connections PrefrontalAssociationCortex Primary Motor Area (M I) THALAMUS (VLm, VAmc, MD) STRIATUM(CaudateNucleus) SNr (Substantia Nigra, pars reticulata) pyramidal tract tract LMN

15. GP, SNr StriatumMotorCortex VA-VLcomplex -- GABA -GABA +glutamate glutamate + glutamate + Basal Ganglia (Microcircuitary) Connections

16. Organization of the motor system Level 1 Thalamus Brain Stem Cerebral cortex motor areas Basal Ganglia Cerebellum Muscle contraction and Movement Sensory receptors Spinal Cord Level 3 Level 2 1. The elements 2. Three levels 3. Feedback loops between and within levels.

17. Disorders Of Basal Ganglia Hyperkinetic – Chorea, Athetosis & Ballism Hypokinetic – Akinesia &Bradykinesia

18. SYDENHAM’S CHOREA - Complication of Rheumatic Fever Rheumatic Fever - Fine, disorganized, and random movements of random movements of extremities, face and extremities, face and tongue tongue - Accompanied by Muscular Hypotonia Muscular Hypotonia - Typical exaggeration of associated movements associated movements during voluntary activity during voluntary activity - Usually recovers spontaneously spontaneously in 1 to 4 months in 1 to 4 months Clinical Feature Principal Pathologic Lesion: Corpus Striatum

19. Clinical Feature Principal Pathologic Lesion: Corpus Striatum (esp. head of caudate nucleus) & Cerebral Cortex Corpus Striatum (esp. head of caudate nucleus) & Cerebral Cortex - Predominantly autosomal dominantly inherited chronic fatal disease inherited chronic fatal disease (Gene: chromosome 4) (Gene: chromosome 4) - Insidious onset: Usually 30-50 - Choreic movements in onset - Frequently associated with emotional disturbances emotional disturbances - Ultimately, grotesque gait and sever dysarthria, progressive dementia dysarthria, progressive dementia ensues. ensues. HUNTINGTON’S CHOREA

20. HEMIBALLISMHEMIBALLISM - Usually results from CVA (Cerebrovascular Accident) (Cerebrovascular Accident) involving subthalamic nucleus involving subthalamic nucleus - sudden onset - Violent, writhing, involuntary movements of wide excursion movements of wide excursion confined to one half of the body confined to one half of the body - The movements are continuous and often exhausting but cease and often exhausting but cease during sleep during sleep - Sometimes fatal due to exhaustion - Could be controlled by phenothiazines and stereotaxic phenothiazines and stereotaxic surgery surgery Clinical Feature Lesion: Subthalamic Nucleus

21. Muhammad Ali in Alanta Olympic Parkinson’s Disease Disease of mesostriatal dopaminergic system PD normal

22. Substantia Nigra, Substantia Nigra, Pars Compacta (SNc) Pars Compacta (SNc) DOPAminergic Neuron Slowness of Movement - Difficulty in Initiation and Cessation of Movement of Movement Clinical Feature (1) Parkinson’s Disease - Paralysis Agitans

23. Clinical Feature (2) Resting Tremor Parkinsonian Posture Rigidity-Cogwheel Rigidity Parkinson’s Disease Paralysis Agitans