Anatomically based guidelines for systematic investigation of the central somatosensory system and their application to a spinocerebellar ataxia type 2 (SCA2) patient

Abstract

Dysfunctions of the somatosensory system are among the clinical signs that characterize a variety of polyglutamine or CAG-repeat diseases. Deficits within this system may hinder the perception of potential threats, be detrimental to somatomotor functions, and result in uncoordinated movements, ataxia, and falls. Despite the considerable clinical relevance of such deficits, however, no systematic pathoanatomical studies of the central somatosensory system in polyglutamine diseases are currently available. The present paper has two goals: (1) recommendation of an economical tissue sampling method and optimized histological processing of this tissue to allow rapid and reliable evaluation of the structural integrity of all known relay stations and interconnecting fibre tracts within this complex system, and (2) the proposal of guidelines for a rapid and detailed pathoanatomical investigative procedure of the human central somatosensory system. In so doing, we draw on the current state of neuroanatomic research and apply the methods and guidelines proposed here to a 25-year-old female patient with spinocerebellar ataxia type 2 (SCA2). The use of 100 microm serial sections through the SCA2 patient's central somatosensory components showed that obvious neuronal loss occurred in nearly all of the relay stations of this system (Clarke's column; cuneate, external cuneate and gracile nuclei; spinal, principal and mesencephalic trigeminal nuclei; ventral posterior lateral and ventral posterior medial nuclei of the thalamus), whereas the majority of interconnecting fibre tracts (dorsal spinocerebellar tract; cuneate and gracile fascicles; medial lemniscus; spinal trigeminal tract, trigeminal nerve and mesencephalic trigeminal tract) displayed signs of atrophy accompanied by demyelinization. These pathological findings suffice to explain the patient's impaired senses of vibration, position and temperature. Moreover, together with the lesions seen in the motor cerebellothalamocortical feedback loop (pontine nuclei, deep cerebellar nuclei and cerebellar cortex, ventral lateral nucleus of the thalamus), they also account for the somatomotor deficits that were observed in the young woman (gait, stance, and limb ataxia, falls, and impaired writing). In proposing these new guidelines, we hope to enable others to study the hitherto unknown morphological counterparts of somatosensory dysfunctions in additional CAG-repeat disease patients.