Differential Diagnosis in Neurology

14.1. Introduction to Movement Disorders

• The basic approach to understanding and diagnosing movement disorders is an attempt to fit them into specific clinically useful major symptom complexes.
• Earlier anatomic pathologic correlations have described a broad outline of specific areas of the brain associated with specific types of movement disorders. It is clear that movements are organized into distributed loops in many ways similar to language and behavioral neurology.
  • The easiest classification is that in which a patient is moving too much, too little and at times hardly at all.
    • Conditions that are characterized by an excess of movement:
      • Hyperkinesia
      • Dyskinesia
      • Combinations
    • Decrease of movement:
      • Akinesia
      • Bradykinesia
      • Decreased automatic movement
      • Not associated with weakness or spasticity
    • The planning of a movement is called an engram. Planning for simple movements has been associated with the pre-motor cortex and the supplementary motor cortex. The engram of tasks that require sequential movements are associated with the posterior parietal lobe.
    • Inability to sustain a sequence of movements "is impersistence persistence" which is right parietal. Inability to progress from one movement to the next to perform a specific task is perseveration and is most often seen with left frontal lesions.
    • Areas that require movement in emotional situations (fear, curiosity, joy) employ a distributed loop in which the caudate nucleus and anterior cingulate gyrus are pivotal.
    • Horizontal and vertical eye movements from the frontal eye fields are initiated, and have complicated connections to the midbrain ocular motor areas, brainstem nuclei, the medial longitudinal fasciculus, multiple areas of the reticular formation, the parapontine RF, the superior colliculus and vestibular nuclei.
    • Self-paced internal movements (tapping a finger to a pre-set pattern) are associated with the supplementary motor area (SMA).
    • Overlearned movements such as walking, turning over in bed, and reflex defensive movements (nocifensor movements) are initiated and coordinated in the basal ganglia.

Specific Correlation of Lesions and Movement Disorders

• Cortex:
  • BA 4: Pyramidal dysfunction
  • BA 6:
    • Hemispheric syndrome of difficulty initiating specific movements or lack of facility with movements and slight weakness
    • Inhibitory strip of Marion Hines. Stimulating of this area inhibits BA 4.
  • Engrams, persistence, impersistence, apraxias, motor relapse phenomena (various grasp and avoidance phenomena)
  • Parietal lesions with "loathness" to move (project to areas 4 and 6)
  • Hand eye coordination BA 5 of the superior parietal cortex projects to hand area and motor cortex. These connections are most important for the use of stereoscopic vision and fine finger movement
  • Corticoreticular myoclonus
• Putamen:
  • Dystonia
  • Cortically initiated pyramidal movements (motor loop)
• Caudate nucleus (anteroventral lesions):
  • Chorea
  • Emotional aspects of movement
• Globus pallidus:
  • Unilateral lesion causes contralateral dystonia, hemiparkinsonism or tremor
  • Bilateral lesions cause flexed posture, rigidity, dystonia, abulia or akinesia
• Red nucleus:
  • Fibers of passage from the dentate are involved with lesions in this area causing a "rubral" tremor:
    • The oscillation of the hand increases on the trajectory to the target
    • Associated postural kinetic tremor
• Substantia nigra:
  • Parkinson's disease
• STN (subthalamic nucleus):
  • 85% destruction of the nucleus causes hemiballismus
  • Proximal musculature more affected than distal
• Reticular formation:
  • Myoclonus (nucleus gigantocellularis)
• Pallidal putaminal lesions:
  • Sudden falling contralaterally while sitting, standing or walking:
    • Slower than falls from lack of tone that occurs with medial RF lesions
    • Lack of postural corrective reflexes
• Lesions of the putamen and internal capsule:
  • Hemiplegic-Parkinsonism
  • Medial reticular formation (tone)
• Locomotor centers (gait):
  • Nucleus cuneiformis of the midbrain activated by the pedunculopontine nucleus and the globus pallidus.
  • Other major components of this loop:
    • Posterior thalamic areas
    • Brainstem areas
    • Basic oscillatory circuits between flexor and extensor spinal cord neurons (step generators)
    • Cerebellum

The Direct and Indirect Pathways

• This hypothesis has made understanding of movement disorders much easier.
• Problems with the hypothesis are :
  • Recurrent collaterals make separation into a direct and indirect loops impossible
  • Earlier histological studies demonstrating distinct patch and matrix systems have a more complex physiology that cannot be easily compartmentalized.
  • Results of surgical procedures do not support clinical findings in every instance.

The Direct System

The putamen and caudate receive excitatory input from the pars compacta of the substantia nigra (D2 receptors) and in turn inhibit the medial globus pallidus and pars reticularis of the substantia nigra (GABA erigic fibers). These neurons then project to VA and VL of the motor thalamus. They utilize GABA which inhibits firing of these thalamic motor neurons (which utilize glutamate) that prevents or lessens firing of cortical neurons. This causes bradykinesia and the inability to sustain movement.

An easy way to remember these functional systems is to figure out the firing of the VA/VL neurons of the motor thalamus. They excite cortical motor neurons and utilize glutamate. If the GABA ergic neurons of the SNpr and GP: internus fire less, less GABA ergic inhibition of thalamic motor neurons occurs, they fire more readily, release glutamate and sustain cortical firing which relieves bradykinesia.

The Indirect System

The putamen and caudate receive inhibitory projections (D1 receptors) from SNpc. They project inhibitory GABA ergic fibers to the lateral GPe. The GPe (lateral globus pallidus) projects inhibitory fibers to the STN (subthalamic nucleus). The STN utilizes glutamate which projects to and stimulates the GPi and the SNpr. Thus stimulating of GPi and SNpr (which is an inhibitory GABA ergic projection) blocks or lessens the firing of VL and decreases cortical motor firing.

The important aspect of this system is that STN utilizes glutamate to stimulate inhibitory neurons of SNpr and GPi. Stimulation of these projection neurons that (utilize GABA) decreases firing of the motor cortex. In akinetic rigid syndromes there is less inhibition of the caudate and putamen due to fewer functioning cells in the substantia nigra pars compacta (SNpc) and therefore, there is more GABA ergic inhibition of the motor cortex.