Anatomy of the Basal Ganglia and Related Structures
For the past 30 years, movement disorders have encompassed the study of a group of conditions characterized by poverty of movement, the akinetic-rigid syndromes, and those with excessive movements, the hyperkinetic movement disorders (tremor, dystonia, myoclonus, chorea/ballism, tics, and others). This traditional view, in which disorders of basal ganglia resulted in the aforementioned syndromes, has now expanded to include the ataxias and disorders of gait and posture. Advances in surgical techniques and imaging studies have broadened the clinical horizon and catchments of the movement disorders specialist. With the increasing indications for botulinum toxin therapy, spasticity and others disorders are now managed by many movement disorders neurologists.
Abnormal involuntary movements (AIMs) should be viewed as clinical signs with many causes. For example, parkinsonism may be the clinical manifestation of a variety of conditions with different or unclear etiolo gies. Defining the broad category of the movement dis order in a given patient precedes the classic approach to neurologic diagnosis: localizing the lesion and determin ing the etiology of the condition. A careful history with particular attention to family background, pregnancy, labor and delivery, early developmental milestones, trauma, infections, medical and psychiatric comorbidities, and use of illicit drugs and medications, especially neuroleptics, are particularly important when first evaluating a patient with abnormal involuntary movements and may suggest the underlying cause. A detailed general medical examination with emphasis on eye movements, presence of KayserFleischer rings (suggesting Wilson disease), and funduscopic examination looking for retinopathy and optic nerve abnormalities (papillitis, papilledema, or optic nerve atrophy suggesting demyelinating diseases, metabolic disorders, or mitochondrial cytopathies); organomegaly (betraying metabolic or storage diseases); and skin discolorations or deposits (defining phakomatosis, xeroderma pigmentosum, vitaminosis, gastrointestinal disease, malabsorption, calcinosis, or cholesterol deposits, especially at the muscle tendons) may prove rewarding. Searching for additional clues, with a carefully performed neurologic examination, will help in the understanding of the patient’s condition.
Once the abnormal movements have been classified, and the neurologic accompaniments documented and placed in context, the cause may become apparent and proper ancillary testing may be undertaken.
ANATOMY OF THE BASAL GANGLIA AND RELATED STRUCTURES
Anatomically, the basal ganglia constitute a complex circuitry that includes neurons of the caudate nucleus, putamen, subthalamic nucleus (STN) globus pallidus, and substantia nigra (SN). The output of the basal ganglia is directed at the motor thalamus (and from there to the frontal cortex) and the pedunculopontine nucleus (PPN).
Globus Pallidus. Divided by the internal medullary lamina into an external (GPe) and internal (GPi) segments, the globus pallidus borders laterally with the putamen, dorsomedially with the internal capsule and optic tract and ventrally with the substantia innominata, which, in turn, contains three major functional anatomic systems: the ventral striatopallidal system, the extended amygdala, and the nucleus basalis of Meynert. The latter nucleus, with its cholinergic andγaminobutyric acid (GABAergic) projections, playsan important role in disorders of memory and the treatment of dementias. The GPi is a major efferent structure of the basal ganglia, using three major projection systems: the ansa lenticularis, the lenticular fasciculus, and the pallidotegmental tract. The ansa lenticularis sweeps ventromedially around the internal capsule, joining the lenticular fasciculus to form the thalamic fasciculus, which, in turn, projects to different thalamic nuclei, especially the ventral anterior (VA), ventral lateral (VL), centromedian, and parafascicular intralaminar nuclei of the thalamus. The pallidotegmental tract terminates in the pedunculopontine nucleus.
Caudate Nucleus. The caudate nucleus resembles an elongated and curved exclamation mark. Its main part is an expanded head directly continuous with a smaller and attenuated body that merges into an elongated tail. The head bulges into the anterior horn of the lateral ventricle and forms its sloping floor. The caudate nucleus is separated from the lentiform nucleus by the anterior limb of the internal capsule, but the separation is incomplete because the head of the caudate nucleus and the putamen are connected, especially anteroinferiorly, by bands of gray matter traversing the white matter of the anterior limb. This admixture of gray and white matter produces the striated appearance that jus tifies the term “corpus striatum” applied to these nuclei.
The head tapers into the narrower body that lies in the floor of the central part of the lateral ventricle, lateral to the superior surface of the thalamus and separated from it by a shallow sulcus lodging the stria terminalis and thalamostriate vein. The tail turns downward along the outer margin of the posterior surface of the thalamus, with the stria terminalis still lying in a slight groove between them. It then curves forward into the roof of the inferior horn of the lateral ventricle, where it separates from the thalamus and lentiform nucleus by the inferior part of the internal capsule and by fibers (including some from the anterior commissure) that spread into the temporal lobe.
Amygdaloid Body. The tail of the caudate nucleus ends in a small, almondshaped expansion, the amygdaloid body, which is a complex of several small nuclei located in the forepart of the roof of the inferior horn of the lateral ventricle. The stria terminalis issues from the amygdaloid body and runs along the medial side of the caudate nucleus until it reaches the vicinity of the ipsilateral interventricular foramen. Here, some of its fibers join the anterior commissure, others pass to the “septal” region adjacent to the lamina terminalis, and the remainder descends to the hypothalamus and anterior perforated substance.
A nuclear midbrain complex, the substantia nigra (SN), is divided into a pigmented and dopaminecontaining pars compacta (SNc) and a cellpoor, pigmentfree pars reticularis (SNr). Most dopaminergic projections go to the striatum, while a smaller proportion of SNc axons terminate in the prefrontal cortex. The SNr is a major primary efferent structure of the basal ganglia, along with GPi. SNr goes primarily to thalamus, PPN, and the superior colliculus.
A biconvex structure, the subthalamic nuclei (STN) receives glutamatergic inputs from the cerebral cortex, GABA inhibition from the GPe, and provides glutama tergic innervations to the GPe, GPi, SN, and PPN. The STN has become a structure of interest because of its pivotal role in our understanding of basal ganglia function.
The postsynaptic dopamine receptors are divided into two major broad categories, D1/D5 and D2, D3, D4 family of receptors, segregated into two main path ways. The direct pathway, subserved by D1 dopamine receptors, sends its projections to the subthalamic nuclei via the GPi, and the indirect pathway, via the D2 family of receptors, influences the STN via the GPe.
Recently, the excitatoryinhibitory interplay between the direct and indirect pathways has been conceptual ized as focused selection and tonic inhibition (surround inhibition hypothesis). By suppressing excitability in an area that is surrounding an activated neural network, neuronal activity focuses to select desired responses. Simultaneously, other pallidal neurons projecting to the thalamus, act to permit desired movements. By decreasing their discharge, through focused striatal output chiefly via the direct pathway, tonic inhibition to the thalamus is removed, releasing the cortical generators for normal or desired movement to occur. Therefore the presence of abnormal involuntary movements results from either failure of inhibition or excessive excitation of the surrounding structures.
Based on the models discussed above, it is important to recognize the pallidum as the major outflow structure of the basal ganglia. Most fugal pathways pass throught the fields of Forel. Presently, the STN is the preferred target for the surgical treatment of idiopathic Parkinson disease (iPD), the ventral intermediate (VIM) thalamus for the treatment of essential and certain other types of tremor, and the GPi for dystonia, with deep brain sti ulation (DBS) being the favored surgical procedure.