Ganong's Review of Medical Physiology, 23rd Edition

254 SECTION III Central & Peripheral Neurophysiology

Treatment

An important consideration in Parkinson disease is the bal-
ance between the excitatory discharge of cholinergic interneu-
rons and the inhibitory dopaminergic input in the striatum.
Some improvement is produced by decreasing the cholinergic
influence with anticholinergic drugs. More dramatic improve-
ment is produced by administration of L-dopa (levodopa).
Unlike dopamine, this dopamine precursor crosses the blood–
brain barrier and helps repair the dopamine deficiency. How-
ever, the degeneration of these neurons continues and in 5 to
7 y the beneficial effects of L-dopa disappear.
Surgical treatment by making lesions in GPi (pallidotomy)
or in the subthalamic nucleus helps to restore the output bal-
ance toward normal (Figure 16–11). Surgical outcomes have
been further improved by implanting electrodes attached to
subcutaneous stimulators and administering high-frequency
current. This produces temporary disruption of circuits at the
electrode tip on demand.
Another surgical approach is to implant dopamine-secret-
ing tissue in or near the basal ganglia. Transplants of the
patient’s own adrenal medullary tissue or carotid body works
for a while, apparently by functioning as a sort of dopamine
minipump, but long-term results have been disappointing.
Results with transplantation of fetal striatal tissue have been
better, and there is evidence that the transplanted cells not
only survive but make appropriate connections in the host’s
basal ganglia. However, some patients with transplants
develop severe involuntary movements (dyskinesias).
In monkeys with experimental parkinsonism, neurotrophic
factors benefit the nigrostriatal neurons, and local injection of
GDNF attached to a lentivirus vector so that it penetrates cells
has produced promising results.

Familial cases of Parkinson disease occur, but these are

uncommon. The genes for at least five proteins can be

mutated. These proteins appear to be involved in ubiquitina-

tion. Two of the proteins, α-synuclein and barkin, interact

and are found in Lewy bodies. The Lewy bodies are inclusion

bodies in neurons that occur in all forms of Parkinson disease.

However, the significance of these findings is still unsettled.

CEREBELLUM

ANATOMIC DIVISIONS

The cerebellum sits astride the main sensory and motor sys-

tems in the brain stem (Figure 16–12). It is connected to the

brain stem on each side by a superior peduncle (brachium

conjunctivum), middle peduncle (brachium pontis), and infe-

rior peduncle (restiform body). The medial vermis and lateral

cerebellar hemispheres are more extensively folded and fis-

sured than the cerebral cortex (Figure 16–13). The cerebellum

weighs only 10% as much as the cerebral cortex, but its surface

area is about 75% of that of the cerebral cortex. Anatomically,

the cerebellum is divided into three parts by two transverse fis-

sures. The posterolateral fissure separates the medial nodulus

and the lateral flocculus on either side from the rest of the cer-

ebellum, and the primary fissure divides the remainder into an

anterior and a posterior lobe. Lesser fissures divide the vermis

into smaller sections, so that it contains 10 primary lobules

numbered I–X from superior to inferior. These lobules are

identified by name and number in Figure 16–13.

ORGANIZATION

The cerebellum has an external cerebellar cortex separated by

white matter from the deep cerebellar nuclei. Its primary

FIGURE 16–11 Probable basal ganglia-thalamocortical
circuitry in Parkinson disease. Solid arrows indicate excitatory outputs
and dashed arrows inhibitory outputs. The strength of each output is in-
dicated by the width of the arrow. GPe, external segment of the globus
pallidus; GPi, internal segment of the globus pallidus; SNC, pars compac-
ta of the substantia nigra; STN, subthalamic nucleus; PPN, peduncu-
lopontine nuclei; Thal, thalamus. See text for details. (Modified from Grafton
SC, DeLong M: Tracing the brain circuitry with functional imaging. Nat Med 1997;3:602.)

Normal

CORTEX

PUTAMEN

SNC

D2

GPe

STN

D1

Brain stem,spinal cord PPN Brain stem,spinal cord

Thal

Parkinsonism

CORTEX

SNC

GPe

STN

PPN

Thal

PUTAMEN

D2 D1

GPi GPi

FIGURE 16–12 Diagrammatic representation of the principal

parts of the brain. The parts are distorted to show the cerebellar pedun-

cles and the way the cerebellum, pons, and middle peduncle form a “nap-

kin ring” around the brain stem. (Reproduced with permission, from Goss CM

[editor]: Gray’s Anatomy of the Human Body, 27th ed. Lea & Febiger, 1959.)

CEREBRUM

Cerebellar

peduncles

Cerebral peduncle

Superior peduncle

Middle peduncle

Inferior peduncle

Medulla oblongata

PONS

CEREBELLUM