Spinocerebellar ataxias (SCAs) are a group of disorders affecting the brain and spinal cord, characterized by progressive loss of coordination of gait accompanied by poor coordination of hands, speech, and eye movements. SCA1 was the first of these ataxias for which the molecular basis was discovered. SCA1 is characterized by progressive cerebellar ataxia, dysarthria, and deterioration of bulbar functions. Early symptoms of the disease include gait disturbance, slurred speech, difficulty in balancing, extremely fast eye movements (saccades), nystagmus, and dysphagia. Later, symptoms get more and more severe, and may include features such as dysmetria, hypotonia, muscle atrophy, cognitive impairment, chorea, dystonia, and bulbar dysfunction. In patients with juvenile onset of the disease, the symptoms are more severe, and the progression to the advanced stages is rapid. However, usually, onset of the disease is in the fourth or fifth decades of life, and it takes about ten years for the condition to reach to its fatal stage.
Diagnosis can be made on the basis of analysis of CT and MRI scans of the brain, which may show atrophy of the branchia pontis and anterior lobe of the cerebellum, along with enlargement of the fourth ventricle. In addition, visual and motor evoked potentials may show abnormality following transcranial magnetic stimulation. The most definitive diagnosis, however, can only be made on the basis of molecular testing of the taaxin-1 gene. There is no cure for the condition. Management is only supportive, and requires consultations with a neurologist, physical and occupational therapists.
SCAI follows an autosomal dominant pattern of inheritance with 95% penetrance. The genetic cause of the condition is mutations in the Ataxin-1 gene. All affected individuals contain an extended CAG repeat in this gene, extending from anywhere between 39 and 91 repeats. Individuals with 36-38 of these repeats remain asymptomatic, albeit with a tendency to have offspring with more number of repeats, and consequently, affected with the disease. Individuals with less than 36 CAG repeats are normal.
Pratap-Chand et al. (1995) described 11 consecutive children with clinical and radiological features of OPCA which started in infancy. In addition to cerebellar ataxia, these children also had sensorineural deafness and speech impairment. Of the present cases, 8 were sporadic and the pedigree patterns in 3 (with a sibling also involved) point to an autosomal recessive inheritance. The CT scan showed varying degrees of cerebellar and pontine atrophy.
Kumar et al. (1995) reported 14 children (equal males and females) with olivopontocerebellar atrophy (OPCA) who were diagnosed between 1990 and 1994 clinically and radiologicaly. All children were clinically examined and investigated (complete blood count, liver and renal functions, CSF examination, immunoglobulins, lipid profile, lactic acid ceruplasmin, and uric acid levels). CT scan axial images of 8 mm thickness were made, but when these were not diagnostic, 4 mm thickness axial images of the posterior fossa were made and graded. Atrophy in each cerebellar hemisphere, vermis, and brain stem were then scored. The criteria used to diagnose OPCA after exclusion of other diseases by laboratory investigations included cerebellar pyramidal or extra-pyramidal involvement, and presence of abnormal CT features (atrophy of cerebellum and midbrain). All patients (except one) had cerebellar ataxia, seven had hypotonia, two had ophthalmoplegia, and two had retinitis pigmentosa. Family history of similar illness in first degree relatives was present in five children while the other nine had no such history. All laboratory investigations were either normal or negative and none of the children had sickle cell disease. CT scan images revealed dilated cerebellar folia in all patients with grade 3 changes in 11, grade 4 in one and grade 5 changes in two patients. There was also a dilated fourth ventricle in all cases with dilated cerebellar folia, five patients had brain stem atrophy, and three had cerebral atrophy. The sum of scores ranged from 4 to 11 according to Gilman scale.
Chand et al. (1996) reported the clinical and radiological features of 17 consecutive Omani patients (eight males and nine females with ages ranging from 9 to 19 years), with olivopontocerebellar atrophy (OPCA) of juvenile onset seen in the period from 1990 to 1994. The diagnostic criteria were progressive cerebellar ataxia and CT scan features of cerebellar and pontine atrophy. A detailed history was taken from all patients, who were thoroughly examined, and investigated with CT scan, brainstem auditory evoked response (BAER), visual evoked response (VER), EEG, nerve conduction studies, CSF examination, urine aminoacidogram, complete hemogram, routine blood biochemistry, serum ceruplasmin, immunoglobulins, lipid profile and lactic acid estimations. Consanguinity was present in ten patients and in nine there was a positive family history. Autosomal dominant inheritance was seen in five and recessive inheritance in four of the patients. The age of onset varied from 5 to 12 years (mean of 8.2 years), and all the patients presented with slowly progressive ataxia, in addition to dysarthria in eight, poor vision in three, seizures in three, and dysphagia in one. Clinically, they had varying degrees of cerebellar, ocular, and motor signs and according to the clinical profile, the patients were divided into three major groups. The first group was composed of eight patients with OPCA and pigmentary retinal degeneration (PRD), in whom the age of onset was 5 to 11 years. In this group, four patients showed autosomal dominant inheritance (two with the mother affected, there was hypoglossal palsies and torticolis in one, in another patient, there was postural hypotension) two showed autosomal recessive inheritance, while the other two were sporadic. In five patients there was cognitive decline while two had generalized seizures. The second group was composed of three patients with distal symmetric sensorimotor peripheral neuropathy (SMPN) with OCPA with dominant inheritance in one (father was affected) and recessive in two. In this group, nerve conduction studies revealed reduced conduction velocities and in one, the sural nerve biopsy showed evidence of axonal degeneration with fall out of large diameter myelinated fibers. The last group was categorized as sporadic and had no distinct neurological deficit. Four of them had in addition to cerebellar ataxia, loss of saccades, and spasticity in lower limbs with one had generalized seizures, and urinary incontinence in another. Another patient in this group had extrapyramidal rigidity and slow rest tremor in the limbs and head, while another had lower cranial nerve palsies with the cerebellar signs. All blood investigations were normal, but the CT scan of the brain revealed varying degrees of cerebellar and pontine atrophy with enlarged fourth ventricle in 11 patients, enlarged cisterna magna in 12 patients and enlarged foramen of Magendie in eight patients. The BAER was absent in two patients, two had absent waves 1 and 2 (due to involvement of cochlear nerve) and in another four, waves 3 and 5 had prolonged latencies (due to brainstem atrophy). On the other hand, the VER in the patients with PRD revealed prolonged latencies and low amplitudes of P100, but similar changes were seen in three other patients with normal looking retina reflecting the subclinical involvement of the visual pathways. EEG revealed generalized seizure discharges in three patients. Chand et al. (1996) found it difficult to classify some of these patients according to the existing system of OPCA classification due to the heterogeneity in the clinical features, and recommended further genetic and molecular studies to identify the underlying cause and the pathophysiology of these childhood onset OPCA seen in Oman.
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