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The abnormal neuronal excitability hypothesized in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine would ameliorate slow saccadic eye movements (SEMs), apathy and hypersomnia in MD patients. SEMs were selected as simple modality for psychomotor investigation. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. SEMs were recorded by electrooculography and analyzed by a computer system. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. Hydroquinidine significantly increased the normalized peak saccadic velocity and shortened the saccadic reaction time compared to placebo. The drug's effects on apathy and hypersomnia are presented in a companion paper.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia that commonly presents with ataxia, slow saccadic eye movements, dysarthria, and peripheral neuropathy. Extremely slow saccades are common but not pathognomonic. The expanded CAG repeat is SCA2 which encodes polyQ in the abnormal gene product, ataxin-2 (see Chap. 98). Normal alleles are between 15 and 32 repeats in length while expanded alleles are 53–77 repeats in length. Together with SCA6, SCA2 is the form most likely to occur sporadically without a positive family history in prior generations. This is believed to be due to further expansion of a modestly enlarged repeat during transmission from one generation to the next.

Spinocerebellar ataxia-type 2 (SCA2) is an autosomal dominant cerebellar ataxia which commonly presents with ataxia, slow saccadic eye movements, dysarthria, and peripheral neuropathy. SCA2 is caused by polyQ-encoding CAG repeat expansions resulting in the production of the abnormal protein, Ataxin-2. Normal alleles are between 15 and 32 repeats in length, while expanded alleles are 53–77 repeats in length. SCA2 differs clinically from SCA1 in that saccadic slowing, hyporeflexia, tremor, and titubation are more pronounced. Among the physical signs observed in SCA2, saccadic slowing is a very characteristic feature which is observed in most patients. About 50% of patients have vertical or horizontal gaze palsy.

This chapter focuses on Spinocerebellar Ataxia type 2 ( SCA2 ) genes. SCA2 was first described clinically as a distinct genetic entity in a large, homogeneous population of patients with dominantly inherited cerebellar ataxia from the Holguin province of Cuba. In this founder population, ataxic gait and other cerebellar findings are universal, and many patients have slow saccadic eye movements. Tendon reflexes are usually brisk during the first years of life, but absent several years later. SCA2 is also particularly common in India. Analysis of a large number of SCA2 pedigrees has indicated a wide range of phenotypic manifestations that make SCA2 indistinguishable from other SCAs in the individual patient, although some findings such as slow saccades, peripheral neuropathy, and dementia are particularly common in SCA2. Identification of the SCA2 gene has led to a definition of the phenotype that includes not only the typical ataxia phenotype, but also rarer parkinsonian phenotypes that may at times be indistinguishable from idiopathic Parkinson's disease.

Article abstract-We report limitation of gaze and slow saccadic eye movements by clinical examination and video-oculography in a patient with Becker muscular dystrophy. This rare association suggests that a dystrophinopathy should be considered in a patient with features characteristic of Becker muscular dystrophy even when mild impairment of eye movements is present. NEUROLOGY 1996;46: 564-566

Slow saccadic eye movements occur in some patients with Huntington's disease (HD), and minor defects of supranuclear eye movement control can be demonstrated in the majority by neuroophthalmological laboratory methods. In the pathogenesis of slowed saccades, a lesion of the paramedian pontine reticular formation and specifically the nucleus pontis centralis caudalis was considered likely due to similar eye movement disturbances in well documented degenerative and vascular lesions of the lower pontine tegmentum. A systematic morphometric study was performed on the nucleus pontis centralis caudalis in 9 patients with HD. Two of them had grossly defective saccades during life, and 7 had normal eye movements on routine examination. In 8 patients, the nucleus was reduced in size, revealed a higher than normal neuronal density, and a striking loss of large neurons. One patient with HD and normal morphometric results had died 2 years after the onset of chorea from an unrelated illness. It is proposed that the nucleus pontis centralis caudalis is regularly affected in HD and that progressive loss of large neurons is the cause of saccadic slowing.

The conditions in which slow saccadic eye movements can be found in normal subjects and neurological patients are discussed.

Four members of a family with spinocerebellar degeneration and slow saccadic eye movements are described. Detailed electrophysiological studies revealed abnormalities of neurological pathways not apparent clinically. The patients had slow saccades as mesasured electrophysiologically, as well as absence of rapid eye movements (REM) despite REM stages of sleep. These studies suggest that although saccadic eye movement and REM are mediated through the pontine paramedian reticular formation, other characteristics of REM sleep are not necessarily mediated through the same neurons.

This is the first reported case of Wilson's disease where a global defect of saccadic eye movements has been documented by electro-oculography. The defect of rapid eye movements is discussed in relation to current anatomical, pathological, and experimental work relating to the descending frontobulbar saccadic eye movement system. It is suggested that the caudate nucleus pathology in Wilson's disease might be responsible for the defect of saccadic movement by interrupting a descending polysynaptic pathway.

The pontine tegmentum contains the neurons responsible for generation of saccadic eye movements and certain phases of sleep. We studied two genetically unrelated patients with spinocerebellar degeneration and slow saccadic eye movements. Multiple all-night sleep studies in both patients disclosed absence of REM and stage 4 sleep with an extremely short stage 3 and long stage 2. Both patients had a sleep stage (X) not previously reported. These are the first awake and ambulatory humans in whom consistent absence of REM sleep has been demonstrated. Both behaved appropriately during wakefulness and showed no overt psychological abnormalities.