SCA-12: Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion.

OBJECTIVE: To characterize the clinical and neuroradiologic features of a new spinocerebellar ataxia, SCA-12, in the index family. BACKGROUND: The authors recently linked SCA-12 to a novel CAG repeat expansion on chromosome 5q31-33 that is located within the 5' region of PPP2R2B, a gene encoding a brain-specific regulatory subunit of protein phosphatase 2A. METHODS: Neurologic features of the proband and nine symptomatic relatives in the first SCA-12 family were compiled and, in some individuals, related to changes found on brain MRI or CT. RESULTS: SCA-12 typically presented in the 4th decade of life with action tremor of the head or arms (present in 10/10 of the affected individuals). Hyperreflexia (8/10) was a common feature, and cerebellar signs (8/10), including ataxia, dysmetria, and dysarthria, developed gradually but were less prominent and disabling than cerebellar dysfunction in other SCA. Subtle parkinsonian features (9/10) and dementia (2/10) were observed in later stages of SCA-12, and psychiatric symptoms, including depression, anxiety, or delusions, were present in some affected family members (4/10). Two individuals studied had nondisabling neurologic signs neonatally, including nystagmus and lower extremity dystonia. Brain images of affected individuals revealed cerebral and cerebellar atrophy. CONCLUSIONS: SCA-12 is a slowly progressive, autosomal dominant, neurodegenerative disorder that differs from other SCA in that it typically presents with action tremor in patients in their mid 30s and usually includes hyperreflexia and subtle parkinsonian signs. Cerebellar dysfunction, including gait ataxia, is relatively nondisabling, and cognitive or psychiatric disorders may occur. Neuroradiologic studies reveal atrophy of the cerebellum and cerebral cortex.

Torsional nystagmus during vertical pursuit.

We examined three patients with cavernous angioma within the middle cerebellar peduncle. Each patient had an unusual ocular motor finding: the appearance of a strong torsional nystagmus during vertical pursuit. The uncalled-for torsion changed direction when vertical pursuit changed direction. In one patient, we recorded eye movements with the magnetic field technique using a combined direction and torsion eye coil. The slow-phase velocity of the inappropriate torsional nystagmus was linearly related to the slow-phase velocity of vertical smooth pursuit, and changed direction when vertical pursuit changed direction. This torsional nystagmus also appeared during fixation suppression of the vertical vestibulo-ocular reflex (VOR), but was minimal during vertical head rotation when fixing a stationary target in the light. We suggest that inappropriately directed eye movements during pursuit might be another ocular motor sign of cerebellar dysfunction. Furthermore, we speculate that the signals used for vertical smooth pursuit are, at some stage, encoded in a semicircular canal VOR coordinate framework. To illustrate, for the vertical semicircular canals, vertical and torsional motion are combined on the same cells, with the anterior semicircular canals mediating upward movements and the posterior semicircular canals mediating downward movements. For the right labyrinth, however, both vertical semicircular canals produce clockwise slow phases (ipsilateral eye intorts, contralateral eye extorts). The opposite is true for the vertical semicircular canals in the left labyrinth; counterclockwise slow phases are produced. Hence, to generate a pure vertical VOR, the anterior or posterior semicircular canals on both sides of the head must be excited so that opposite-directed torsional components cancel. Thus, if pursuit were organized in a way similar to the VOR, pure vertical pursuit would require that oppositely-directed torsional components cancel in normals. If this did not happen, a residual torsional nystagmus could appear during attempted vertical pursuit.

Visual parameters in patients with pituitary adenoma before and after transsphenoidal surgery.

Eighty-two patients with pituitary adenoma who underwent transsphenoidal surgery were examined before and after surgery. Nineteen patients had a normal preoperative neuro-ophthalmological examination. All of these patients maintained normal visual parameters postoperatively. The remaining 63 patients had tumour-related loss of visual acuity, visual field, or both. These patients ranged in age from 18 to 78 years. Duration of symptoms ranged from one day to ten years, with a median of six months. Preoperative visual acuity was 6/12 or better in 72% of eyes, with 90% of patients having 6/12 or better in their better eye. Only 7% of eyes had a normal preoperative visual field. Both visual acuity and visual field improved postoperatively in the majority of eyes. In eyes that were examined within one week after surgery and subsequently, substantial improvement occurred within the first postoperative week, but further improvement continued over weeks to months postoperatively, with visual field taking longer to stabilise than visual acuity. Visual acuity at last examination was 6/12 or better in 87% of eyes, and visual field at last examination was normal in 50% of eyes. A total of 92% of patients had visual acuity of 6/12 or better in their better eye, and 62% of patients had a normal visual field in their better eye. Visual acuity at last examination was correlated with both age and preoperative visual acuity. Last visual field also was correlated with both age and preoperative visual field. Patients with preoperative optic atrophy had a poorer visual prognosis than did patients with normal fundi.

Aggravation of myasthenia gravis by erythromycin.

Erythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction.

Processing of the 5' end of Escherichia coli 16S ribosomal RNA.

We have isolated and partially characterized an endonuclease involved in processing the 5' end of 16S rRNA of Escherichia coli. A mutant strain that is deficient in this enzyme accumulates a new precursor of 16S rRNA, named 16.3S rRNA. This rRNA has the 3' end of mature 16S rRNA but is about 60 nucleotides longer at the 5' end. In vitro, the enzyme preparation cleaves an RNA fragment of about 60 nucleotides from the 5' end of 16.3S rRNA in 30S ribosomal subunits, yielding the mature 5' end of 16S rRNA. In the mutant strain the 16.3S rRNA is associated with a full complement of 21 ribosomal proteins in 30S subunits. These particles, which comprise 50% of the total 30S subunits, are present on polyribosomes.