Degeneration of ingestion‐related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7

Abstract

Dysphagia, which can lead to nutritional deficiencies, weight loss and dehydration, represents a risk factor for aspiration pneumonia. Although clinical studies have reported the occurrence of dysphagia in patients with spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3), type 6 (SCA6) and type 7 (SCA7), there are neither detailed clinical records concerning the kind of ingestive malfunctions which contribute to dysphagia nor systematic pathoanatomical studies of brainstem regions involved in the ingestive process. In the present study we performed a systematic post mortem study on thick serial tissue sections through the ingestion-related brainstem nuclei of 12 dysphagic patients who suffered from clinically diagnosed and genetically confirmed spinocerebellar ataxias assigned to the CAG-repeat or polyglutamine diseases (two SCA2, seven SCA3, one SCA6 and two SCA7 patients) and evaluated their medical records. Upon pathoanatomical examination in all of the SCA2, SCA3, SCA6 and SCA7 patients, a widespread neurodegeneration of the brainstem nuclei involved in the ingestive process was found. The clinical records revealed that all of the SCA patients were diagnosed with progressive dysphagia and showed dysfunctions detrimental to the preparatory phase of the ingestive process, as well as the lingual, pharyngeal and oesophageal phases of swallowing. The vast majority of the SCA patients suffered from aspiration pneumonia, which was the most frequent cause of death in our sample. The findings of the present study suggest (i) that dysphagia in SCA2, SCA3, SCA6 and SCA7 patients may be associated with widespread neurodegeneration of ingestion-related brainstem nuclei; (ii) that dysphagic SCA2, SCA3, SCA6 and SCA7 patients may suffer from dysfunctions detrimental to all phases of the ingestive process; and (iii) that rehabilitative swallow therapy which takes specific functional consequences of the underlying brainstem lesions into account might be helpful in preventing aspiration pneumonia, weight loss and dehydration in SCA2, SCA3, SCA6 and SCA7 patients.

Differential Progression of Dysphagia in Heredity and Sporadic Ataxias Involving Multiple Systems

“…A pathological study reported that the solitary nucleus, a viscerosensory nucleus associated with swallowing, cardiovascular regulation, and respiration, was affected in MSA [20]. In contrast, another report described that neurodegeneration of the solitary nuclei was relatively mild in SCA3, as compared with other nuclei including the ambiguus nucleus [21], a visceromotor nucleus also severely affected in MSA [22]. One relatively large-scale study demonstrated that the pre-Bötzinger complex in the medulla oblongata was severely affected in non-dysphagic patients with MSA, whereas it was spared in dysphagic patients with SCA3 [23].…”

Brain pathology of spinocerebellar ataxias

“…Subsequent to its onset in childhood or mid adulthood, SCA3 has a severe impact on the quality and length of life [137,154]. The brain pathology in SCA3 is severe and widespread.…”

“…Age of onset varies from early childhood to late adulthood, and very long CAG expansions ([200) result in disease onset at infancy [2,3,155]. The progressive symptoms severely impact quality and length of life [137].…”

“…6) [15]. Microscopic analyses reveal widespread neuronal loss in the cerebral cortex, basal ganglia, thalamus, midbrain, pons, medulla oblongata and cerebellum ( 98,134,135,137,138,140,141,[143][144][145].…”

The Multiple Faces of Spinocerebellar Ataxia type 2

“…Neurons of dorsal root ganglia and Clarke columns are reduced in number. There is degeneration of posterior funiculi and dorsal spinocerebellar tracts 33, 34. Sural nerve biopsy shows a loss of myelinated fibers even in the absence of clinical signs of peripheral neuropathy 35…”