ABSTRACT
Although the cranial nerves, their nuclei and related fiber tracts are crucial for a variety of oculomotor, somatomotor, somatosensory, auditory, vestibular-related, autonomic and ingestion-related functions, knowledge regarding the extent of their involvement in spinocerebellar ataxia type 2 (SCA2) patients is incomplete. Accordingly, we performed a pathoanatomical analysis of these structures in six clinically diagnosed SCA2 patients. Unconventionally thick serial sections through the brainstem stained for lipofuscin pigment (aldehyde-fuchsin) and Nissl material (Darrow red) showed that all oculomotor, somatomotor, somatosensory, auditory, vestibular and autonomic cranial nerve nuclei may undergo neurodegeneration during SCA2. Similarly, examination of myelin-stained thick serial sections revealed that nearly all cranial nerves and associated fiber tracts may sustain atrophy and myelin loss in SCA2 patients. In view of the known functional role of the affected cranial nerves, their nuclei and associated fiber tracts, the present findings provide appropriate pathoanatomical explanations for some of the disease-related and unexplained symptoms seen in SCA2 patients: double vision, gaze palsy, slowing of saccades, ptosis, ingestion-related malfunctions, impairments of the optokinetic nystagmus and the vestibulo-ocular reaction, facial and tongue fasciculation-like movements, impaired centripetal transmission of temperature-related information from the face, dystonic posture of the neck, as well as abnormalities of the brainstem auditory evoked potentials.
Subject(s)
Brain Stem/pathology , Cranial Nerves/pathology , Spinocerebellar Ataxias/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Nerve Degeneration/pathology , Spinocerebellar Ataxias/physiopathologyABSTRACT
A total of 59 relatives of patients suffering from Cuban Dominant Cerebellar Ataxia (SCA2) were studied, undergoing physical examination in order to evaluate them clinically as well as by studies of peripheral nerve conduction. Clinical manifestations were detected in 13 of these patients. In 11 other patients there were electrophysiological alterations without symptoms or signs. The main electrophysiological alterations detected were reduced amplitude of the sensitive potentials. This is an expression of an axonal lesion occurring at a presymptomatic stage.
Subject(s)
Cerebellar Ataxia/physiopathology , Neural Conduction/physiology , Peripheral Nerves/physiopathology , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/genetics , Cuba , Electrophysiology , HumansABSTRACT
A total of 59 relatives of patients suffering from Cuban Dominant Cerebellar Ataxia (SCA2) were studied, undergoing physical examination in order to evaluate them clinically as well as by studies of peripheral nerve conduction. Clinical manifestations were detected in 13 of these patients. In 11 other patients there were electrophysiological alterations without symptoms or signs. The main electrophysiological alterations detected were reduced amplitude of the sensitive potentials. This is an expression of an axonal lesion occurring at a presymptomatic stage.
ABSTRACT
The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 12q24.1. A 1.1-megabase contig in the candidate region was assembled in P1 artificial chromosome and bacterial artificial chromosome clones. Using this contig, we identified a CAG trinucleotide repeat with CAA interruptions that was expanded in patients with SCA2. In contrast to other unstable trinucleotide repeats, this CAG repeat was not highly polymorphic in normal individuals. In SCA2 patients, the repeat was perfect and expanded to 36-52 repeats. The most common disease allele contained (CAG)37, one of the shortest expansions seen in a CAG expansion syndrome. The repeat occurs in the 5'-coding region of SCA2 which is a member of a novel gene family.
Subject(s)
Chromosomes, Human, Pair 12 , Proteins/genetics , Spinocerebellar Degenerations/genetics , Trinucleotide Repeats , Amino Acid Sequence , Ataxins , Base Sequence , Chromosome Mapping , DNA, Complementary/isolation & purification , Gene Expression Regulation , Humans , Molecular Sequence Data , Nerve Tissue Proteins , Sequence Analysis, DNA , Sequence Homology, Amino AcidABSTRACT
We describe 263 patients with autosomal dominant cerebellar ataxia from the Holguín province, Cuba. There is evidence of a common ancestry and the population represents the largest homogeneous group of patients yet described. Primary features include gait ataxia, dysarthria, dysmetria, adiadochokinesia, cramps, tremor, hypotonia, abnormal reflexes, and slowed/limited eye movements. Age at onset ranged from 2 to 65 years. There was considerable clinical variability within the families. No patients had optic atrophy, spasticity, pigmentary retinal degeneration, or cogwheel rigidity, and only 1 had dementia.