Tremor pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

It is thought that tremor is the result of a combination of different mechanisms that could result in oscillatory/rhythmic movement. These mechanisms are mechanical oscillations, reflex oscillations, central oscillations, and cerebellar oscillation. These mechanisms differ on the basis of their origin.

The normal physiology of tremor is based on the four oscillatory centers: ^[1][2][3]

• Mechanical oscillations: Occurs in limbs, could be limited to a particular joint
• Reflex oscillations: Originates from afferent muscle spindles
• Central neuronal pacemaker: Involves thalamus, basal ganglia, inferior olive.
• Cerebellar Oscillations: Disturbance in feedforward or feedback loops in cerebellum resulting in oscillations.

• It is understood that tremor is the result of oscillations produced by the above-mentioned mechanisms.
• The following are some common causes of tremor and the mechanisms from which they originate: ^[1]

• Essential tremor is transmitted in an autosomal dominant pattern. So far, no particular genes have been identified as the cause. In Linkage study, three susceptible loci were mapped in families with pure monogenic essential tremor: ^[4]
  • 3q13
  • 2p25-p22
  • 6p23
• Wilson’s disease is transmitted in an autosomal recessive pattern. ^[5]
  • Mutation in the ATP7B gene on chromosome 13 (13q14.3)

Conditions associated with tremor include:

• Parkinson’s disease
• Drug-induced parkinsonism:Neuroleptics, metaclopromide,phenothiazines
• Wilson’s disease
• Metabolic disorders: Thyrotoxicosis, pheochromocytoma, hypoglycemia
• Alcohol withdrawal
• Peripheral Neuropathy
• Orthostatic tremor
• Essential tremor

On gross pathology, Parkinson’s disease has loss of dopamine pigment in the substantia nigra.

On microscopic histopathological analysis, Lewy bodies and Lewy neurites are found in neuronal cell bodies and neuronal cell processes, respectively in patients with Parkinson’s disease.