MINISTRY OF HEALTH OF UKRAINE

VINNYTSIA NATIONAL MEDICAL UNIVERSITY

NAMED AFTER M.I.PYROGOV

NEUROLOGY DEPARTMENT

Stomatology Faculty

Lesson # 4

Cerebellum. Extrapyramidal System.

1. Basic questions:

1.1. Cerebellum. Surface Anatomy:

1.2. Cerebellum. Internal Structure:

1.3. Connections of the Cerebellum with Other Parts of the Nervous System:

1.4. Cerebellar Function and Cerebellar Syndromes:

1.5. Components of the Basal Ganglia.

1.6. Connections of the Basal Ganglia.

1.7. Basal Ganglia Neurotransmitters:

1.8. Basal Ganglia Diseases: Loss of Nigrostriatal Pathway:

a) Parkinson’s disease

1.9. Basal Ganglia Lesions in Striatum and Subthalamic Nucleus:

a) dyskinesias, athetoid movements, ballismus, choreiform movements.

b) Huntington’s disease.

2. Literature:

Mathias Baehr, M.D., Michael Frotscher, M.D. Duus’ Topical Diagnosis in Neurology. – P.240-259, 330-358

Mark Mumenthaler, M.D., Heinrich Mattle, M.D. Fundamentals of Neurology. – P.78, 80, 127-136.

Cerebellum

The cerebellum is a central organ for fine motor control. It processes information from multiple sensory channels (particularly vestibular and proprioceptive), together with motor impulses, and modulates the activity of motor nuclear areas in the brain and spinal cord.

Anatomically, the cerebellum is made up of two hemispheres and the vermis that lies between them. It is connected to the brainstem by the three cerebellar peduncles. An anatomical section reveals the cerebellar cortex and the underlying white matter, in which the deep cerebellar nuclei are embedded. The cerebellar cortex is primarily responsible for the integration and processing of afferent impulses. It projects to the deep cerebellar nuclei, which then emit most of the efferent fibers that leave the cerebellum.

Functionally (and phylogenetically), the cerebellum is divided into three components: the vestibulocerebellum, spinocerebellum, and cerebrocerebellum. The vestibulocerebellum is phylogenetically oldest. It receives afferent input mainly from the vestibular organ, and its function is to regulate balance. The spinocerebellum mainly processes proprioceptive impulses from the spinocerebellar pathways and controls stance and gait. The youngest component of the cerebellum, the cerebrocerebellum, has a close functional relationship with the motor cortex of the telencephalon and is responsible for the smooth and precise execution of all finely controlled movements.

Cerebellar lesions manifest themselves clinically with disturbances of movement and balance.

Surface Anatomy

The cerebellum lies in the posterior fossa. Its superior surface is covered by the tentorium cerebelli, a tentlike double fold of the dura mater that separates the cerebellum from the cerebrum.

The surface of the cerebellum (Fig. 5.1), unlike that of the cerebrum, displays numerous small, horizontally running convolutions (folia), which are separated from each other by fissures. The narrow central portion of the cerebellum connecting the two hemispheres on either side is called the vermis because of its fancied resemblance to a worm.

A view of the cerebellum from below (Fig. 5.2) reveals the upper portion of the fourth ventricle lying between the cerebellar peduncles. The fourth ventricle communicates with the subarachnoid space through a single median aperture (foramen of Magendie) and two lateral apertures (foramina of Luschka). Caudal to the inferior and middle cerebral peduncles, there is a structure on either side called the flocculus; the two flocculi are connected across the midline through a portion of the vermis called the nodulus. Together, these structures constitute the flocculonodular lobe.

The subdivisions of the cerebellar vermis and hemispheres were given individual names by the old anatomists (culmen, declive, etc.), which are indicated in Figs. 5.1 and 5.2, although they have little functional significance and are generally not clinically relevant. Today, it is more common to distinguish three major components of the cerebellum on phylogenetic and functional grounds:

The archicerebellum (phylogenetically oldest portion of the cerebellum) is intimately related to the vestibular apparatus. It receives most of its afferent input from the vestibular nuclei of the brainstem and is thus also called the vestibulocerebellum. Anatomically, it consists mainly of the flocculus and nodulus (flocculonodular lobe).

The paleocerebellum (next oldest portion of the cerebellum, after the archicerebellum) receives most of its afferent input from the spinal cord and is, therefore, also called the spinocerebellum (the term we will use in the following sections). It consists of the culmen and central lobule of the anterior lobe of the vermis, as well as the uvula and pyramid of its inferior lobe, and the paraflocculus. One can state, as a mild simplification, that the spinocerebellum is composed of most of the vermis and paravermian zone (pars intermedialis).

The neocerebellum (youngest portion of the cerebellum) is its largest part. Its phylogenetic development occurred together with the expansion of the cerebrum and the transition to an upright stance and gait. It is formed by the two cerebellar hemispheres and has an intimate functional connection to the cerebral cortex, which projects to it by way of the pontine nuclei. Thus, the neocerebellum is also termed the pontocerebellum or cerebrocerebellum, as we will call it in the following sections.

Internal Structure

Although the cerebellum accounts for only about 10% of the brain by weight, it contains more than 50% of all the brain’s neurons. The neurons of the cerebellum are located in the gray matter of the highly convoluted cerebellar cortex and in the four deep cerebellar nuclei on either side.

Cerebellar Cortex

The cerebellar cortex is composed of three layers (Fig. 5.3). Proceeding from the outermost inward, these layers are:

Molecular layer (stratum moleculare). This layer consists mainly of cellular processes, of which the majority are granule cell axons—parallel fibers, see below— and Purkinje cell dendrites. A few neurons are found among the fibers (stellate cells, basket cells, Golgi cells), which function as inhibitory interneurons.

Pukinje cell layer (stratum ganglionare). This thin layer contains nothing but the large cell bodies of the Purkinje cells, arranged side by side in rows. The elaborate, highly branched dendritic trees of these cells are directed outward into the molecular layer, where the dendritic tree of each individual Purkinje cell lies in a plane perpendicular to the long axis of the folium. The Purkinje cell axons are the only efferent fibers leaving the cerebellar cortex. They project mainly to the deep cerebellar nuclei and release the inhibitory neurotransmitter GABA (γ-aminobutyric acid). Efferent fibers from the cortex of the vestibulocerebellum bypass the deep cerebellar nuclei and project directly to sites outside the cerebellum.

Granulecell layer (stratumgranulosum).This layer consists almost entirely of the densely packed cell bodies of the small granule cells, which account for more than 95% of all cerebellar neurons. The axons of these cells are mainly found in the molecular layer, where they travel along individual folia as parallel fibers and form synapses with the perpendicularly oriented dendritic trees of the Purkinje cells (approximately 200000 parallel fibers form synapses with a single Purkinje cell). The cerebellar granule cells are glutamatergic and are the only neurons of the cerebellar cortex that exert an excitatory influence on their target cells.

Afferent Input to the Cerebellar Cortex

The afferent input to the cerebellar cortex is mainly derived from the ipsilateral vestibular nuclei (a small part, in fact, comes directly from the vestibular organ,

without any intervening synaptic relay), the ipsilateral spinal cord, the contralateral pontine nuclei (and thus, indirectly, from the contralateral cerebral cortex), and the contralateral olivary nuclear complex in the medulla (olive, for short). The olivary fibers are the so-called climbing fibers, which terminate on the Purkinje cells of the cerebellar cortex, climbing up their dendritic trees like ivy. All other afferent fibers terminate as mossy fibers on the granule cells of the cerebellar cortex, which then relay further impulses along their axons (parallel fibers of the molecular layer) to the Purkinje cell dendrites. Both mossy fibers and climbing fibers give off important collaterals to the deep cerebellar nuclei on their way to the cortex. In view of the fact that both the mossy fibers and the granule cells (and thus the overwhelming majority of synapses in the cerebellum) are glutamatergic, it is not surprising that the administration of glutamate antagonists causes a marked worsening of cerebellar function in patients with cerebellar lesions.

Cerebellar Nuclei

A horizontal section of the cerebellum reveals four deep nuclei within each cerebellar hemisphere (see Fig. 5.5).

The fastigial nucleus (“roof nucleus”) is found most medially, in the roof of the fourth ventricle. It receives most of its afferent fibers from the Purkinje cells of the flocculonodular lobe (vestibulocerebellum). Its efferent fibers travel directly to the vestibular nuclei (fastigiobulbar tract) (Fig. 5.5) or cross to the opposite side of the cerebellum and then continue to the reticular formation and the vestibular nuclei (uncinate fasciculus).

Lateral to the fastigial nucleus, one finds two smaller nuclei, the globose nucleus (usually divided into two or three subnuclei) and the emboliform nucleus. Both of these nuclei receive afferent input from the cortex of the paravermian zone and vermis (spinocerebellum) and send efferent fibers to the contralateral red nucleus (Fig. 5.5).

The largest of the cerebellar nuclei, the dentate nucleus, occupies a lateral position in the deep white matter of each cerebellar hemisphere. Its afferent input comes mainly from the cortex of the cerebellar hemispheres (cerebrocerebellum), and, to a lesser extent, from the cortex of the paravermian zone. Its efferent fibers travel by way of the superior cerebellar peduncle to the contralateral red nucleus and thalamus (ventral lateral nucleus, VL) (Fig. 5.5).

The thalamus is the site of a synaptic relay, with further projection to the motor areas of the cerebral cortex (Brodmann areas 4 and 6).

Afferent and Efferent Projections of the Cerebellar Cortex

and Nuclei

Synaptic transmission within the cerebellum follows a uniform scheme (Fig. 5.4): the cerebellar afferent pathways project to the cerebellar cortex and, through collateral fibers, to the deep cerebellar nuclei. In the cortex, afferent information is processed in a complex polysynaptic pathway that eventually converges onto the Purkinje cells. The Purkinje cells, in turn, transmit the results of this processing to the deep cerebellar nuclei, in the form of inhibitory, GABAergic impulses. In the deep nuclei, integrative processing of both primary information (from the collateral fibers of the cerebellar afferent pathways) and modulated information (from the Purkinje cells/from the cortex) takes place and the result is then transmitted, by way of cerebellar efferent fibers, to the targets of the cerebellar projections.

Connections of the Cerebellum

with Other Parts of the Nervous System

All sensory modalities that are important for orientation in space (vestibular sense, touch, proprioception, vision, and hearing) convey information to the cerebellum. The cerebellum receives input from widely diverse sensory areas of the nervous system by way of the three cerebellar peduncles, and sends its output by way of the deep cerebellar nuclei to all motor areas. The more important pathways are shown schematically in Fig. 5.5.

Inferior Cerebellar Peduncle

The inferior cerebellar peduncle (restiform body) contains the following afferent pathways:

1) Fibers from the vestibulocochlear nerve and the vestibular nuclei to the flocculonodular lobe and fastigial nucleus (Fig. 5.5).

2) Axons from the contralateral olive in the olivocerebellar tract, which continue as climbing fibers to the dendrites of the Purkinje cells of all areas of the cerebellar cortex.

3) The posterior spinocerebellar tract, whose fibers arise in the neurons of the nucleus dorsalis (thoracic nucleus or Clarke’s column) at the base of the posterior horn of the spinal gray matter; this tract mainly conveys impulses from the muscle spindles of the lower limbs and trunk to the paravermian zone of the anterior and posterior lobes.

4) Fibers from the reticular formation (not shown in Fig. 5.5).

The inferior cerebellar peduncle contains the following efferent pathways:

1) The fastigiobulbar tract (largest efferent pathway of the inferior cerebellar peduncle) to the vestibular nuclei; this tract closes a vestibulocerebellar regulatory feedback loop through which the cerebellum influences the motor function of the spinal cord.

2) Fibers from the fastigial nucleus to the reticular formation (cerebelloreticular tract) and from the dentate nucleus to the olive (cerebello-olivary tract).

Middle Cerebellar Peduncle

The middle cerebellar peduncle (brachium pontis) exclusively contains afferent fibers, of the following types:

1) The pontocerebellar tract decussates in the pons and then travels in a thick bundle, by way of the middle cerebellar peduncle, to the cerebellar hemispheres. These fibers originate in the basal pontine nuclei and are thus the continuation, after a synaptic relay, of the corticocerebellar projections, which are derived from all of the lobes of the cerebrum, but in greatest number from the frontal lobe. The fibers cross the midline as soon as they emerge from the relay nuclei in the basis pontis.

2) Further afferent fibers from the monoaminergic raphe nuclei travel by way of the middle cerebellar peduncle to the cerebellum.

Superior Cerebellar Peduncle

Efferent pathways. The superior cerebellar peduncle (brachium conjunctivum) contains most of the cerebellar efferent fibers. These fibers originate in the deep cerebellar nuclei and project mainly to the following structures:

1) The contralateral thalamus (ventral lateral and centromedian nuclei) Efferent fibers to the thalamus. Efferent fibers in the superior cerebellar peduncle traveling to the thalamus arise mainly in the dentate nucleus (cerebrocerebellum). After a synaptic relay in the thalamus, further fibers ascend to the motor and premotor cerebral cortex, which, in turn, projects back to the pontine nuclei by way of the corticopontine tract. A long regulatory loop is thus created, traveling from the cerebral cortex to the pontine nuclei, cerebellar cortex, dentate nucleus, thalamus, and finally back to the cortex (Figs 5.5 and 5.6).

2) The contralateral red nucleus

3) The reticular formation

Efferent fibers to the red nucleus and reticular formation. A further regulatory circuit comprises the so-called triangle of Guillain and Mollaret, traveling from the red nucleus by way of the central tegmental tract to the olive, then to the cerebellum and back to the red nucleus (Fig. 5.7). The cerebellum influences spinal motor function byway of fibers traveling from the red nucleus and reticular formation down into the spinal cord.

Afferent pathways. One of the few afferent pathways in the superior cerebellar peduncle is

1) the anterior spinocerebellar tract, which terminates in the same area (spinocerebellum) as the posterior spinocerebellar tract. Both convey proprioceptive impulses from the periphery, i.e., from muscle spindles, Golgi tendon organs, and joint receptors.