The neuropsychological approach to remediation emphasizes the use of intact areas of higher cortical functioning in the development of remedial strategies while minimizing the emphasis placed upon dysfunctional cortical areas. This investigation was directed towards evaluating the effectiveness of the neuropsychological approach to the remediation of developmental dyslexia in school age children previously placed in self-contained classrooms for the learning disabled due to reading failure. A significant improvement in word recognition skills was demonstrated with a simitar, but nonsignificant, trend noted in reading comprehension.
MR images of three patients with Leigh9s disease (subacute necrotizing encephalomyelopathy) were compared with CT findings. In all patients typical lesions in the basal ganglia were identified with both MR and CT. In two patients MR permitted identification of additional lesions not detected with CT. In one patient progression of MR abnormalities over a 4-month period correlated well with clinical deterioration in neurologic status. T2-weighted images with a repetition time (TR) greater than 1950 msec and an echo time (TE) greater than or equal to 60 msec or inversion-recovery images with a 50-msec TE, 1213-msec inversion time, and 3000-msec TR were advantageous in identifying multiple necrotic lesions in the brainstem, deep gray matter, periventricular white matter, and cerebral cortex. In this series MR was more sensitive in detecting and localizing multifocal necrotic lesions of Leigh9s disease than CT was, and thus may be a useful diagnostic tool for patients with the appropriate clinical and laboratory abnormalities.
Objective: To describe a clinical syndrome of cerebellar ataxia associated with muscle coenzyme Q10 (CoQ10) deficiency. Background: Muscle CoQ10 deficiency has been reported only in a few patients with a mitochondrial encephalomyopathy characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures, ataxia, mental retardation), and 3) ragged-red fibers and lipid storage in the muscle biopsy. Methods: Having found decreased CoQ10 levels in muscle from a patient with unclassified familial cerebellar ataxia, the authors measured CoQ10 in muscle biopsies from other patients in whom cerebellar ataxia could not be attributed to known genetic causes. Results: The authors found muscle CoQ10 deficiency (26 to 35% of normal) in six patients with cerebellar ataxia, pyramidal signs, and seizures. All six patients responded to CoQ10 supplementation; strength increased, ataxia improved, and seizures became less frequent. Conclusions: Primary CoQ10 deficiency is a potentially important cause of familial ataxia and should be considered in the differential diagnosis of this condition because CoQ10 administration seems to improve the clinical picture.
Subdural empyema is in itself an uncommon complication of infection in childhood and localization of the infection to the parafalcine area is rare. This paper presents a case study of a teenager with subdural empyema resulting from paranasal sinusitis, who presented as a parafalcine syndrome and was treated successfully without neurosurgical intervention. Results of repeat neuropsychological evaluation (premorbid, 17 days into treatment, and after six months), correlated with changes seen on serial CT scanning during treatment and follow up. More importantly, the neuropsychological evaluation was clinically more sensitive than the traditional neurological examination in assessing changes in cortical integrity during the course of recovery. Thus, neuropsychological evaluation proved to be a valuable supplement to the neurological examination in exploring morbidity and assisting in treatment decision making in the management of subdural empyema.
The neurodegenerative diseases of infancy and childhood include disorders in which there is progressive loss of neurological function due to structural abnormalities of the central nervous system. Well over six hundred disorders, many of which are rarely seen, can be included in this category. Yet, the conditions represent collectively over one-fourth of all admissions to pediatric neurology services. Five-year samples of admission characteristics of 1218 patients from two medical centers over twenty-two years permit an estimate of the frequency of the neurodegenerative diseases. The six most-encountered diagnoses, in declining order, were: subacute sclerosing panencephalitis; neuronal ceroid lipofuscinosis; tuberous sclerosis with degeneration; West disease, or idiopathic degenerative encephalopathy associated with infantile spasms; Werdnig-Hoffmann disease, and hereditary spastic paraplegia. A classification is offered grouping the neurodegenerative disorders into five major categories: polioencephalopathies, leukoencephalopathies, corencephalopathies, spinocerebellopathies, and diffuse encephalopathies. Disorders in each subgroup may be either genetic or nongenetic. Neurodegenerative diseases have multiple causes, including metabolic, viral, immunopathic, environmental, and epileptogenic. The cause of many remains unknown.
Oxidative phosphorylation (OXPHOS) diseases can be caused by mutations in nuclear genes or mitochondrial DNA (mtDNA) genes. mtDNA mutations include complex mtDNA rearrangements in which large segments of mtDNA are duplicated or deleted and point mutations in which single nucleotide substitutions occur within transfer RNA (tRNA) genes, ribosomal RNA (rRNA) genes, or mitochondrial genes encoding OXPHOS polypeptides. Although over 30 pathogenic mtDNA point mutations and over 60 different types of mtDNA deletions are known (Shoffner and Wallace, 1995; Wallace et al., 1994), only a subset of these mutations are associated with cerebellar ataxia. This review focuses on the clinical, biochemical, and genetic features of OXPHOS diseases caused by mtDNA mutations in which ataxia is a common manifestation.
Subacute necrotizing encephalopathy (SNE) or Leigh9s disease is associated with various defects in oxidative phosphorylation (OXPHOS). However, the relationships between these OXPHOS defects and nuclear DNA or mitochondrial DNA (mtDNA) mutations is still unclear. We evaluated three SNE pedigrees (two singleton cases and a pedigree) biochemically for OXPHOS abnormalities and genetically for four mtDNA point mutations. There was a complex I defect in ail three pedigrees that was associated with a complex III defect in two individuals. An mtDNA mutation in the ATPase, subunit 6 gene (np 8993) was present in one SNE pedigree. This mutation was maternally inherited, heteroplasmic, produced marked clinical and biochemical heterogeneity between pedigree members, and varied along the maternai lineage at levels ranging from 0% to >95% of the total mtDNAs. These mtDNA mutations were not present in the other two pedigrees. These observations emphasize the importance of screening for OXPHOS defects and mtDNA mutations in SNE cases.
Serum carnosinase deficiency (McKusick 21220) is a rare condition, described in 13 cases. Ten additional individuals with serum carnosinase deficiency have been identified. All continued to excrete increased amounts of carnosine in their urine despite a meat-free diet for 3 days. Serum carnosinase activity ranged from 0-30% of normal. In four individuals a normal Km for carnosine of 0.12 mM was observed, while in five individuals an increased Km was found. Homocarnosine levels in CSF in three individuals ranged from 3.4 to 15 mM. Clinical symptoms in these individuals were as follows: attention deficit disorder: 4; non progressive developmental delay: 1; neurofibromatosis: 1; absences seizures: 1; severe, but non-progressive mental retardation, seizures and neurosensory hearing loss: 1; progressive childhood dementia; 1; clinically normal: 1. There was no correlation between severity and type of the neurological symptoms and residual serum carnosinase activity. Although a definite conclusion can only be made after a considerably higher number of individuals has been analyzed, the suspicion that serum carnosinase deficiency is unrelated to the neurological symptoms is strengthened by these observations. There may, however, be an association with a predisposition for mental deficiency.
